Non-Small Cell Lung Cancer Recurrent and Metastatic Disease: Evidence-Based Clinical Summary

On this page

Quick Reference

RxDrug of choiceOsimertinib 80 mg daily for EGFR-mutant NSCLC; pembrolizumab 200 mg IV every 3 weeks for PD-L1 ≥50% without driver alterations

AltAlternativesAumolertinib 110 mg daily + platinum-pemetrexed for EGFR-mutant; sunvozertinib 300 mg daily for EGFR exon20ins; poziotinib 16 mg daily for HER2 exon20ins; lazertinib 240 mg daily + SBRT for oligometastatic EGFR-mutant

⊘AvoidNon-dihydropyridine CCBs (diltiazem, verapamil) in EGFR-mutant patients, avoid; bevacizumab added to osimertinib for T790M+ progression (no benefit, increased toxicity); concurrent chemotherapy with reirradiation (adds toxicity without clear benefit); SBRT for ultra-central tumors outside clinical trials

DxTest of choicePET/CT for initial detection of suspected recurrence; tissue biopsy with repeat molecular profiling (EGFR, ALK, ROS1, BRAF, MET, RET, NTRK, KRAS, PD-L1); tumor-informed ctDNA MRD testing for early relapse detection

ScKey scoreALBI grade (albumin-bilirubin), grade 1 best prognosis on anti-PD-1 therapy; grade 2 HR 1.60, grade 3 for OS

→When to referRadiation oncology for SBRT or reirradiation; neurosurgery for brain metastases; palliative care for symptom management; clinical trial for patients with progression on standard therapy

Recurrent NSCLC requires repeat molecular profiling to guide therapy; isolated locoregional recurrence may be curable with salvage surgery or reirradiation; distant disease is managed with biomarker-directed systemic therapy (osimertinib ± chemo or ramucirumab, sunvozertinib, poziotinib, pembrolizumab); oligometastatic disease (≤5 lesions) benefits from SBRT added to targeted therapy or immunotherapy; CNS-penetrant agents and double-dose osimertinib are key for brain metastases.

Recurrent or metastatic non-small cell lung cancer (NSCLC) carries a poor prognosis, but the emergence of targeted therapies and immune checkpoint inhibitors has transformed outcomes for patients with actionable drivers. The pattern of recurrence, local, regional, or distant, dictates the salvage strategy: isolated locoregional relapse may be curable with surgery or reirradiation, while distant disease requires systemic therapy guided by repeat molecular profiling. Oligometastatic disease (≤5 lesions) represents a distinct subset where metastasis-directed therapy with stereotactic body radiotherapy (SBRT) can prolong progression-free survival. This page provides a structured approach to evaluation and management, emphasizing biomarker-directed therapy, CNS-penetrant agents, and the integration of local therapies.

Overview and Recommendations

Background

•Recurrent NSCLC after initial curative-intent therapy (surgery, radiation, or chemoradiation) is classified by disease extent: local (same lobe), regional (ipsilateral hilum, mediastinum, or supraclavicular nodes), or distant (contralateral lung, pleura, liver, brain, bone). The pattern determines the salvage approach, isolated locoregional recurrence may be amenable to aggressive local therapy, while distant relapse almost always requires systemic treatment.
•The risk of recurrence is driven by tumor biology: intratumor copy-number heterogeneity (HR 4.9), visceral pleural invasion (5-year DFS 53.3% vs 65.9% without), and non-inflamed immune phenotype (KEAP1/STK11 co-mutations). ALK-positive NSCLC carries a high risk of brain relapse; adjuvant ensartinib 225 mg daily for 24 months reduced 24-month disease recurrence from 46.5% to 13.6% (HR 0.20).
•Molecular drivers evolve under selective pressure from prior therapy. Repeat biopsy (tissue or plasma ctDNA) is essential to identify resistance mechanisms (e.g., EGFR T790M after first-generation TKIs, bypass-track activation, or histologic transformation) and to detect new actionable alterations (EGFR, ALK, ROS1, BRAF V600E, METex14, RET, NTRK, KRAS G12C). PD-L1 expression may also change.
•Oligometastatic disease, defined as ≤5 lesions in ≤3 organs (NCCN) or ≤3 lesions (ESMO), represents a prognostically favorable subset. Metastasis-directed therapy with SBRT or resection can delay systemic therapy escalation and improve outcomes. The ABLATE trial in EGFR-mutant NSCLC showed that adding SBRT to lazertinib 240 mg daily extended median PFS to 34.0 months vs 24.8 months with lazertinib alone.
•Approximately 50% of patients with stage III NSCLC treated with chemoradiotherapy plus durvalumab will recur; of those, 72% have oligorecurrence (≤3 lesions). The most common sites are lung (34%) and brain (26%), and salvage local therapy significantly improves survival after recurrence (OS2).

Evaluation

•Suspect recurrence in any patient with treated NSCLC who develops new respiratory symptoms (cough, dyspnea, hemoptysis), constitutional symptoms (weight loss, fatigue), or neurologic deficits (headache, seizure, focal weakness). Routine surveillance imaging (CT chest with contrast) is performed every 3-6 months for the first 2-3 years, then annually.
•If CT findings are equivocal, or if there is clinical suspicion despite negative CT, order [18F]FDG PET/CT. PET/CT has significantly higher sensitivity (88% vs 62% for CT) for detecting recurrence, especially after chemoradiotherapy (100% vs 46%) and within the first 6 months after treatment (83% vs 41%). Specificity is lower (89% vs 96%) due to post-radiation inflammation.
•When imaging suggests recurrence, obtain histologic confirmation via image-guided core needle biopsy (CT or ultrasound) or endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) for mediastinal/hilar lesions. A negative biopsy in a high-suspicion lesion should prompt repeat biopsy or multidisciplinary discussion.
•Perform repeat molecular profiling on the rebiopsy specimen: test for EGFR, ALK, ROS1, BRAF V600E, MET exon 14 skipping, RET, NTRK, KRAS G12C, and PD-L1 (22C3 or comparable assay). Resistance mutations (e.g., EGFR T790M) guide subsequent TKI selection. If tissue is insufficient, consider plasma ctDNA testing.
•Assess circulating tumor DNA (ctDNA) for molecular residual disease (MRD) and early relapse detection. Tumor-informed ctDNA assays (e.g., PROPHET) have a median lead time of 299 days to radiologic recurrence. In the LUNGCA-1 cohort, ctDNA positivity at postoperative day 3 or month 1 predicted relapse (HR 11.1), and MRD-positive patients who received adjuvant therapy had improved RFS (HR 0.3).
•Calculate the albumin-bilirubin (ALBI) grade as a simple prognostic tool. ALBI grade 2 vs 1 is associated with HR 1.60 for OS on anti-PD-1 therapy; grade 3 vs 1 with. This readily available lab value stratifies survival even in patients with ECOG PS 1-3 and can inform treatment decisions.
•For patients with isolated brain recurrence, obtain dedicated brain MRI with contrast. If leptomeningeal metastases are suspected, perform lumbar puncture for CSF cytology and ctDNA analysis.
•Evaluate performance status (ECOG PS), time to recurrence (postoperative recurrence has better prognosis than de novo stage IIIB/IV), and prior treatment history (platinum-free interval, prior TKI use, prior immunotherapy). These factors determine the intensity and choice of salvage therapy.

Management

•For isolated local recurrence after SABR or surgery, consider salvage surgery if R0 resection is feasible. Salvage pneumonectomy after high-dose CRT (≥60 Gy) yields median DFS of 14 months; 90-day mortality is 0% for pneumonectomy and 24% for lobectomy. Favorable outcomes are associated with recurrence >12 months after CRT and R0 resection.
•For local-regional recurrence not amenable to surgery, offer reirradiation with SBRT (preferred) or proton therapy. SBRT to a BED₁₀ ≥100 Gy achieves 2-year local failure of ~21.6% and median OS. Adhere to composite dose constraints: esophagus Dmax <120 Gy, lung V20 <40%, heart V40 <50%, spinal cord Dmax <57 Gy. Avoid concurrent chemotherapy with reirradiation if possible.
•For patients with EGFR-mutant metastatic recurrence and no prior third-generation TKI, start osimertinib 80 mg daily. Consider adding platinum-pemetrexed (4-6 cycles) if CNS metastases are present (FLAURA2: HR 0.58 for CNS progression). Alternatively, add ramucirumab 10 mg/kg IV every 3 weeks (RAMOSE: PFS 24.8 vs 15.6 months; NNT ≈7 at 12 months).
•For EGFR exon 20 insertion mutations in platinum-pretreated patients, use sunvozertinib 300 mg once daily (cORR 47.2%, median DOR 13.8 months). Monitor for grade ≥3 diarrhea (18%). For HER2 exon 20 insertions, poziotinib 16 mg once daily is an option (ORR 27.8%, median PFS 5.5 months) but carries high rates of rash (48.9%), diarrhea (25.6%), and stomatitis (24.4%) requiring dose reductions.
•For CNS-dominant recurrence in EGFR-mutant disease, escalate osimertinib to 160 mg daily (double dose). This achieves intracranial disease control rate of 92.5% and complete response rate of 12.5% in leptomeningeal metastases, with median OS 13.3 months. Alternatively, consider proton craniospinal irradiation (pCSI) which improved CNS PFS (7.5 vs 2.3 months) and OS (9.9 vs 6.0 months) compared to photon involved-field RT.
•For PD-L1-positive (≥1%) NSCLC with untreated brain metastases (5-20 mm, asymptomatic, no corticosteroids), treat with pembrolizumab 10 mg/kg every 2 weeks (brain metastasis response rate 29.7%). No responses are seen in PD-L1-negative patients.
•For oligometastatic disease (≤5 lesions) in treatment-naïve EGFR-mutant NSCLC, add SBRT to all metastatic sites (20 Gy in 1 fraction, 30 Gy in 3 fractions, or 35 Gy in 5 fractions) to lazertinib 240 mg once daily. The ABLATE trial showed median PFS of 34.0 months with no grade ≥3 radiation pneumonitis.
•For oligometastatic NSCLC without driver mutations, consider SBRT to all sites before or concurrent with immunotherapy. The PEMBRO-RT trial showed that SBRT (3 × 8 Gy) to a single tumor site before pembrolizumab improved ORR from 18% to 36%, especially in PD-L1-negative patients. The SKYROCKET trial reported median PFS of 9.3 months with SBRT + atezolizumab + tiragolumab.
•Do not use non-CNS penetrant first-generation EGFR TKIs (gefitinib, erlotinib) for patients with brain metastases if osimertinib is available. Avoid adding bevacizumab to osimertinib for T790M-positive patients after progression on first/second-generation TKIs (WJOG8715L showed no PFS benefit and increased toxicity). Avoid SBRT for ultra-central tumors outside clinical trials due to ~15% risk of grade 5 hemoptysis.
•Refer all patients with recurrent or metastatic NSCLC to a multidisciplinary tumor board for discussion of salvage local therapy, clinical trial enrollment, and palliative care integration. For patients with brain metastases, involve neurosurgery for consideration of surgical resection or stereotactic radiosurgery, and radiation oncology for whole-brain RT or pCSI if indicated.
•Monitor patients every 3 months with CT chest/abdomen/pelvis and brain MRI if CNS disease is present. Reassess molecular profile at progression. For patients on immunotherapy, monitor for immune-related adverse events (pneumonitis, colitis, hepatitis, endocrinopathies). Discontinue therapy if unacceptable toxicity or confirmed radiographic progression.

Board Review — High Yield

•Pattern of recurrence determiner, Isolated locoregional recurrence after SABR can be salvaged with surgery or reirradiation and yields 5-year OS similar to patients without recurrence (57.9% vs 54.9%). Distant recurrence requires systemic therapy.
•PET/CT superior to CT, Sensitivity 88% vs 62% for detecting recurrence, especially after chemoradiotherapy (100% vs 46%) and within 6 months (83% vs 41%). False positives from inflammation.
•ctDNA MRD, Tumor-informed ctDNA predicts relapse a median of 299 days before imaging; MRD-positive patients benefit from adjuvant therapy (HR 0.3).
•ALBI grade, Simple liver function index (albumin-bilirubin) that independently predicts OS on anti-PD-1 therapy: grade 2 HR 1.60, grade 3.
•FLAURA2, Adding platinum-pemetrexed to osimertinib reduces CNS progression in EGFR-mutant NSCLC (HR 0.58 for CNS progression; 24-month cumulative incidence 9% vs 23%).
•Ramose trial, Adding ramucirumab to osimertinib prolongs PFS (24.8 vs 15.6 months; HR 0.55); NNT ≈7 at 12 months.
•Sunvozertinib for EGFR exon20ins, 300 mg daily yields cORR 47.2%; effective in brain metastases (52.4% ORR in patients with baseline CNS lesions).
•Double-dose osimertinib (160 mg) for leptomeningeal metastases, Intracranial disease control rate 92.5%, median OS 13.3 months.
•ABLATE trial, SBRT to all sites (≤5 lesions) + lazertinib 240 mg daily in EGFR-mutant oligometastatic NSCLC: median PFS 34.0 vs 24.8 months; no grade ≥3 radiation pneumonitis.
•Ultra-central tumors contraindication, SBRT for ultra-central NSCLC carries ~15% risk of grade 5 hemoptysis; reserve for clinical trials.

Deep Dive — Evidence Details

Patterns of Recurrence

▸Recurrence pattern (local, regional, distant) drives the management algorithm for recurrent NSCLC.
▸GGO-dominant adenocarcinomas have a negligible risk of nodal and distant recurrence, supporting omission of mediastinal LND.
▸Brain metastases are a common and debilitating pattern; CNS-penetrant targeted therapy can delay intracranial progression.

HY High Yield: In patients with GGO-dominant lung adenocarcinoma (CTR ≤0.5, tumor ≤3 cm), systematic mediastinal lymph node dissection can be safely omitted because the risk of nodal metastasis is zero [7].

Recurrence pattern, local, regional, or distant, determines the subsequent management strategy for patients with previously treated NSCLC. The site and extent of relapse reflect the initial tumor biology, the adequacy of prior local therapy, and the effectiveness of systemic treatment. Understanding these patterns enables clinicians to select appropriate surveillance strategies and tailor salvage therapy.

Local and Regional Recurrence

Local recurrence refers to relapse at the primary tumor site after surgical resection or definitive radiotherapy. Regional recurrence involves the ipsilateral hilum, mediastinum, or supraclavicular lymph nodes. After , video-assisted thoracoscopic surgery ( ) and open lobectomy demonstrate comparable locoregional recurrence rates ^[2]^A1a. Systematic mediastinal lymph node dissection (LND) or sampling is standard for early-stage NSCLC, but in patients with ground-glass opacity (GGO)-dominant lung adenocarcinoma, the risk of mediastinal lymph node metastasis is negligible: a phase 3 trial (ECTOP-1009) found no lymph node metastases in 151 patients undergoing systematic LND, and no recurrence events occurred in either arm at interim analysis ^[7]^A1b. These data support selective LND for GGO-dominant tumors. For patients treated with ( ) for early-stage NSCLC, the incidence of regional recurrence is comparable to that after surgery, despite less invasive nodal staging, and occult nodal metastases increase the risk ^[10]^B2a.

Distant Recurrence

Distant (systemic) recurrence includes hematogenous spread to the contralateral lung, pleura, liver, adrenal glands, bone, and brain. The brain is a particularly common and debilitating site: from NSCLC are associated with shortened survival, impaired quality of life, and increased healthcare costs ^[11]^B2a. Prophylactic cranial irradiation (PCI) reduces the incidence of brain metastases in patients with non-metastatic NSCLC, but its impact on overall survival is less clear than in small-cell lung cancer ^[20]^A1b. The FLAURA2 study demonstrated that osimertinib plus platinum-pemetrexed chemotherapy delays CNS progression compared with osimertinib monotherapy in EGFR-mutated advanced NSCLC, with a CNS progression hazard ratio of 0.58 (95% CI 0.33 to 1.01) ^[6]^A1b. This underscores the importance of CNS-penetrant agents in preventing or delaying brain relapse.

Factors Influencing Recurrence Pattern

Several factors predict the pattern of recurrence:

Tumor biology and molecular drivers: Intratumor heterogeneity, particularly copy-number heterogeneity, is strongly associated with recurrence or death (HR 4.9, P=4.4×10⁻⁴) ^[14]^B2b. ALK-positive NSCLC has a high risk of distant and brain relapse; adjuvant ensartinib 225 mg once daily for 24 months improved 24-month disease-free survival from 53.5% to 86.4% (HR 0.20, 95% CI 0.11 to 0.38) ^[15]^A1b.
Surgical approach: VATS lobectomy may reduce systemic recurrence compared with open lobectomy ^[2]^A1a.
Adjuvant therapy: Adjuvant pazopanib in stage I NSCLC did not significantly improve recurrence-free survival (3-year RFS 76% vs 83%, HR 1.3, 95% CI 0.6-2.7) ^[8]^B2b.
Tumor histology: GGO-dominant adenocarcinomas have a very low risk of nodal and distant recurrence ^[7]^A1b.

The pattern of recurrence, locoregional versus distant, directly guides the choice between local consolidative therapy (e.g., re-resection, SBRT, or ) and systemic therapy. The next section details the recommended workup to confirm recurrence and characterize its extent.

Pearl: The recurrence pattern after initial therapy is the single most important determinant of salvage strategy: isolated locoregional relapse may be amenable to aggressive local therapy, while distant recurrence almost always requires systemic treatment, often with consideration of CNS-penetrant agents if brain metastases are present.

Workup of Suspected Recurrence

▸Contrast-enhanced CT is the principal anatomic investigation for suspected recurrence; compare with baseline and prior treatment imaging. [22]
▸Use FDG PET/CT when CT is indeterminate, disease extent is uncertain, or distant disease would change management; interpret uptake in the context of treatment-related inflammation. [22,28]
▸Use brain MRI for neurologic symptoms or suspected intracranial disease; enlarging post-SRS lesions may require multidisciplinary assessment to distinguish recurrence from radiation necrosis. [36]
▸Obtain tissue confirmation when imaging is equivocal or when pathology would alter systemic or local treatment. [22]
▸ctDNA/MRD is promising for early risk detection, with reported positive predictive values of 91.3% and 92.8% in one cohort, but it does not replace imaging or biopsy. [29,33,37,117]
▸Radiomics and artificial-intelligence models remain investigational and should not be used as stand-alone tests. [31,32,113,114,118]

Dx Diagnostic Essentials: Do not label recurrence from a single equivocal scan or ctDNA result when confirmation would change management; integrate serial imaging, treatment history, multidisciplinary review, and biopsy when feasible. [22,29,33,36]

CP Clinical Pearl: For suspected local failure after SABR, reviewing the recurrence against the original dose distribution can distinguish in-field from out-of-field disease and may clarify whether apparent progression represents treatment effect or true recurrence. [30]

Initial clinical assessment

Suspected recurrence should be evaluated in the context of the original stage, histology, molecular profile, treatment modality, interval since definitive therapy, prior sites of disease, new symptoms, and treatment-related complications. The American College of Radiology (ACR) provides evidence-based recommendations for imaging patients treated for stage I–III non-small-cell lung cancer (NSCLC), including those with suspected recurrence or progression. ^[22]^A1c Clinical assessment should determine whether the concern is intrathoracic recurrence, metastatic disease, or a treatment-related mimic, and should guide selection of additional imaging and tissue sampling. ^[22]^A1c

Cross-sectional imaging

Contrast-enhanced chest computed tomography (CT), generally extended to the upper abdomen when clinically indicated, is the principal anatomic test for evaluating suspected thoracic recurrence and progression after treatment. ^[22]^A1c CT should be compared with the pretreatment study, the post-treatment baseline, radiation-treatment plans when available, and all interval examinations. ^[22]^A1c Interpretation must account for expected postoperative, post-radiation, and post-ablation changes, because these may resemble recurrent tumor. ^[22]^A1c In patients treated with stereotactic ablative radiotherapy (SABR), recurrence assessment may be improved by matching follow-up PET/CT findings with the SABR plan and dose distribution to distinguish in-field from out-of-field failure. ^[30]^B2b

The ACR guideline addresses the appropriate use of CT, PET/CT, magnetic resonance imaging (MRI), and combinations of modalities for surveillance and suspected recurrence. ^[22]^A1c A 2025 secondary analysis of the SUPE_R randomized trial compared CT with [18F]FDG PET/CT for recurrence detection in patients with stage IA–IIIC NSCLC who had completed curative-intent treatment; the study directly informs the relative diagnostic performance of these modalities, although modality selection remains dependent on the clinical question and imaging context. ^[28]^A1b

FDG PET/CT and suspected metastatic disease

[18F]FDG PET/CT is useful when CT findings are indeterminate, when recurrence is suspected but its extent is unclear, or when distant disease would alter management. ^[22]^A1c PET/CT can provide whole-body metabolic and anatomic assessment and may identify unsuspected nodal, osseous, adrenal, or other distant disease; suspicious findings should be interpreted with awareness of inflammatory and treatment-related FDG uptake. ^[22]^A1c PET/CT was incorporated into the treatment-planning and recurrence-pattern assessment of patients receiving SABR for unresectable locally advanced NSCLC, supporting its role in defining disease distribution and subsequent failure location. ^[30]^B2b

PET/CT should not automatically replace diagnostic CT or tissue confirmation when a potentially curable isolated recurrence is being considered. ^[22]^A1c A metabolically or anatomically suspicious lesion should be sampled when the result would change treatment, particularly when imaging cannot reliably distinguish recurrence from infection, inflammation, fibrosis, radiation injury, or a second primary malignancy. ^[22]^A1c

Brain and neurologic evaluation

Patients with neurologic symptoms or clinical concern for intracranial progression require brain MRI, with contrast when appropriate, because MRI is the key modality for evaluating suspected brain metastases and treatment response. ^[22]^A1c An enlarging lesion after stereotactic radiosurgery may represent recurrent brain metastasis or radiation necrosis, and conventional imaging alone may be insufficient for distinction. ^[36]^B2b Qualitative MR perfusion is one potential adjunct, but multidisciplinary review outperformed qualitative MR perfusion for distinguishing recurrence from radiation necrosis in the reported NSCLC control cohort; complex cases should therefore undergo multidisciplinary interpretation rather than reliance on a single imaging feature. ^[36]^B2b

Tissue confirmation and pathologic reassessment

Biopsy should be directed toward the safest, most accessible lesion that is representative of the suspected recurrence and likely to provide adequate material for histologic and molecular reassessment. ^[22]^A1c Confirmation is particularly important before initiating systemic therapy, reirradiation, ablation, or another local salvage strategy when imaging is equivocal or when a new primary or benign treatment effect remains plausible. ^[22]^A1c The risk–benefit of percutaneous biopsy should be individualized; a 2025 retrospective study specifically examined recurrence outcomes after percutaneous transthoracic needle biopsy before sublobar resection for stage I lung cancer, underscoring that procedural decisions may have oncologic as well as diagnostic implications. ^[115]

Circulating tumor DNA and molecular residual disease

Post-treatment circulating tumor DNA (ctDNA) is an emerging adjunct, not a replacement for imaging or biopsy. ^[33]^B2a^[37]^B2b^[117]^C An updated meta-analysis of 30 studies involving 3,287 postoperative patients evaluated ctDNA-based molecular residual disease (MRD) for recurrence detection and survival prediction, but emphasized heterogeneity in study design, assay strategy, and statistical power. ^[33]^B2a In the prospective multicenter LUNGCA cohort, serial plasma sampling was performed preoperatively, at postoperative day 3 and 1 month, and every 3–6 months for up to 3 years in 233 patients; the study evaluated dynamic ctDNA for postoperative management. ^[37]^B2b A separate validation study assessed a tissue-informed personalized assay in stage 0–III NSCLC, while an updated 261-patient surgical cohort reported positive predictive values of 91.3% for landmark MRD and 92.8% for longitudinal MRD, with a median lead time of 5.2 months before clinically evident recurrence. ^[117]^C^[29]^C4 These findings support ctDNA as a risk-stratification and early-warning tool, but a positive result should prompt clinical and radiologic evaluation rather than establish recurrence in isolation. ^[33]^B2a^[29]^C4

Emerging computational tools

Radiomics, machine learning, PET-derived metrics, and artificial-intelligence models may help estimate recurrence risk, but they are not established stand-alone diagnostic tests for suspected recurrence. ^[31]^B2a^[32]^B2a^[113]^[114]^[118] Systematic reviews identified promising predictive performance but also methodological limitations and risk of bias; external validation and clinical utility remain important requirements. ^[31]^B2a^[32]^B2a Investigational approaches include preoperative FDG PET SUVmax-based models, 4DCT delta-radiomics, and computer-assisted nodule analysis in patients treated with SBRT. ^[113]^[114]^[118] These tools should supplement, not replace, multidisciplinary review, conventional imaging, and pathology. ^[22]^A1c^[31]^B2a^[32]^B2a

Multidisciplinary decision-making

The final workup should integrate symptoms, serial CT, PET/CT when indicated, brain MRI when clinically warranted, biopsy results, prior radiation dose distributions, and molecular findings. ^[22]^A1c^[30]^B2b^[36]^B2b This approach is especially important for suspected oligorecurrence, post-radiation abnormalities, brain lesions after radiosurgery, and cases in which local salvage, systemic therapy, or reirradiation is being considered. ^[22]^A1c^[36]^B2b^[45]^B3b

Practical investigation pathway

Clinical question	Preferred investigation	Important limitation
Suspected thoracic or regional recurrence	Contrast-enhanced CT with comparison to prior studies and treatment plans	Postoperative and post-radiation changes may mimic recurrence. ^[22]^A1c^[30]^B2b
Indeterminate CT or concern for occult distant disease	[18F]FDG PET/CT	FDG uptake is not cancer-specific; correlate with anatomy and clinical context. ^[22]^A1c^[28]^A1b
Neurologic symptoms or suspected brain metastasis	Contrast-enhanced brain MRI when appropriate	Post-SRS recurrence and radiation necrosis may remain difficult to distinguish. ^[22]^A1c^[36]^B2b
Imaging abnormality that would change treatment	Image-guided biopsy of the safest representative lesion	Procedural risks and adequacy for molecular testing must be considered. ^[22]^A1c^[115]
Molecular risk or early-warning assessment	Serial ctDNA/MRD testing as an adjunct	Positive or negative results should not replace radiologic or pathologic assessment. ^[29]^C4^[33]^B2a^[37]^B2b^[117]^C

Local-Regional Recurrence

▸Classify recurrence as isolated, oligorecurrent, or polyrecurrent; oligorecurrence has been defined as **≤3 lesions amenable to local therapy**, while another study used **≤3 extracranial organs and ≤5 extracranial lesions** for limited recurrence. [41][48]
▸Thoracic reirradiation may improve outcomes in selected patients but requires composite dosimetry, careful patient selection, and multidisciplinary review because severe or fatal toxicity is possible. [40]
▸After lung SBRT, radiation fibrosis can obscure recurrence; MRI with diffusion-weighted and dynamic contrast-enhanced sequences is a studied adjunct, not a universally established replacement for conventional surveillance. [42]
▸Salvage SABR, proton reirradiation, and surgery may offer curative-intent treatment for selected isolated recurrences. [40][51][52][55][122]
▸Multicourse thoracic radiation is feasible only in highly selected patients and carries clinically important pneumonitis risk, including rare grade 5 toxicity. [46][50]

Dx Diagnostic Essentials: Radiation fibrosis may mimic local recurrence after SBRT. Correlate serial CT/PET findings with clinical course and multidisciplinary review; consider biopsy when feasible before definitive salvage treatment. [42][43]

! Warning: Do not apply reirradiation or combined systemic-radiation strategies without reviewing prior plans and cumulative organ-at-risk doses; severe pneumonitis and other high-grade or fatal toxicities have been reported. [40][50][121]

CP Clinical Pearl: Potentially curable local-regional recurrence should be assessed at a multidisciplinary tumor board, particularly when surgery, proton reirradiation, SABR, or multimodality treatment is being considered. [40][49][52][55]

Management Guide for Treating Isolated Local Recurrence (iLR) and Isolated Regional Recurrence (iRR) After Stereotactic Ablative Radiotherapy (SABR) for Early-Stage Non–Small Cell Lung Cancer The workup involves positron emission tomography with computed tomography, magnetic resonance imaging of the brain, endobronchial ultrasound (if applicable based on findings of imaging), liver function tests, complete blood cell count, basic metabolic panel, and pulmonary function tests (if surgery is consi — Figure 1. — Management Guide for Treating Isolated Local Recurrence (iLR) and Isolated Regional Recurrence (iRR) After Stereotactic Ablative Radiotherapy (SABR) f...Europe PMC ↗

Clinical context and recurrence patterns

Local-regional recurrence includes relapse at the treated primary site, regional lymph nodes, or within/near a previous thoracic radiation field after definitive surgery, radiotherapy, stereotactic ablative radiotherapy (SABR), or chemoradiotherapy (CRT). Management should distinguish potentially curable isolated or oligorecurrent disease from polyrecurrent or metastatic progression and should be determined in a multidisciplinary setting. ^[40]^A1c^[41]^B2b^[43]^B2b^[48]^B3b

After SABR for early-stage NSCLC, isolated local recurrence (iLR) or isolated regional recurrence (iRR) occurs in approximately 1 in 6 patients, although salvage outcomes and optimal treatment depend on recurrence site, prior therapy, patient fitness, and the feasibility of definitive local treatment. ^[43]^B2b In a real-world cohort of 166 patients with unresectable stage III NSCLC treated with definitive CRT followed by durvalumab, recurrence patterns and outcomes were assessed by classifying disease as oligorecurrent when there were ≤3 lesions amenable to local therapy or as polyrecurrent disease; the study specifically evaluated post-progression salvage strategies and overall survival. ^[41]^B2b Driver mutation status may influence recurrence patterns and the potential value of local therapy after CRT; one retrospective study classified relapse as in-field recurrence, out-of-field recurrence, or distant metastasis and defined limited recurrence as disease confined to the brain or involving ≤3 extracranial organs and ≤5 extracranial lesions. ^[48]^B3b

Diagnostic evaluation and surveillance

Post-treatment imaging can be difficult to interpret because radiation-induced fibrosis may mimic or obscure local recurrence, particularly after lung SBRT. ^[42]^C4 In a prospective study of 30 patients, a thoracic MRI protocol incorporating diffusion-weighted imaging and dynamic contrast-enhanced imaging was evaluated for assessment of treated lung parenchyma after SBRT; the study was designed to determine feasibility for distinguishing benign post-radiation change from recurrence. ^[42]^C4 Suspicious radiographic progression should therefore be interpreted with serial imaging, metabolic imaging when appropriate, and multidisciplinary review; tissue confirmation is preferred when feasible before initiating major salvage treatment, although the cited studies do not establish a single diagnostic algorithm. ^[42]^C4^[43]^B2b^[55]^C4

Relapse surveillance remains clinically important after definitive CRT. A retrospective analysis of stage III NSCLC evaluated relapse timing, symptomatic versus surveillance-detected presentation, and associations with overall survival, reflecting uncertainty regarding the optimal frequency of follow-up imaging. ^[54]^B3b

Definitive local salvage

For selected patients with isolated intrathoracic recurrence, definitive thoracic reirradiation can improve local control and survival, but treatment carries substantial risks because previously irradiated organs may receive high cumulative doses. The American Radium Society systematic review and guidelines evaluated studies published through May 2020 and issued consensus recommendations regarding patient selection, treatment strategy, radiation technique, and composite dose constraints intended to reduce high-grade or fatal toxicity. ^[40]^A1c Reirradiation should therefore be considered only after review of prior radiation plans, cumulative dose to organs at risk, recurrence geometry, interval from prior treatment, performance status, pulmonary reserve, and competing systemic disease. ^[40]^A1c^[55]^C4

Proton reirradiation is a potential approach for isolated or locoregionally recurrent disease because its dose distribution may reduce exposure of previously irradiated organs. In a prospective multi-institutional study, 57 patients with recurrent NSCLC in or near a prior radiation field were treated at three proton centers; 52 patients (93%) completed the planned treatment, and safety, feasibility, toxicity, and survival were evaluated. ^[55]^C4 A phase 2 trial subsequently examined consolidation pembrolizumab after 60–70 Gy proton reirradiation delivered for locoregional recurrence; pembrolizumab began 4–12 weeks after reirradiation in patients without progression and was continued for up to 12 months, with progression-free survival as the primary endpoint and overall survival and toxicity as secondary outcomes. ^[119]

SABR may be appropriate for small, technically suitable isolated lung recurrences. A prospective phase 2 study enrolled patients with histologically confirmed, PET-staged isolated recurrence or a lung-parenchymal metastasis measuring ≤3 cm and treated them with image-guided SABR to 50 Gy in 4 fractions. ^[122] Retrospective salvage-SBRT series have also included patients previously treated with EBRT, SBRT, surgery, or combinations of these modalities, with imaging follow-up generally performed every 2–3 months. ^[51]^C4 Multicourse lung SBRT has demonstrated high local control in selected patients but can cause clinically significant pneumonitis, including rare fatal toxicity; in one 44-patient series, local control was 91%, grade ≥2 pneumonitis occurred in 13.6%, grade ≥3 pneumonitis in 4.5%, and one patient experienced grade 5 pneumonitis. ^[50]^C4 Even more intensive retreatment may be feasible in highly selected patients: a retrospective study evaluated patients receiving at least 3 definitive thoracic radiation courses for recurrent or metachronous NSCLC, although the evidence remains retrospective. ^[46]^C4

Salvage surgery

Salvage pulmonary resection can provide a potentially curative option for carefully selected patients with persistent or recurrent locoregional disease after definitive nonsurgical therapy. Candidates require multidisciplinary assessment of technical resectability, cardiopulmonary reserve, absence of uncontrolled distant disease, and the morbidity of operating in previously irradiated tissue. ^[49]^B3b^[52]^C4 Salvage surgery has been reported after chemotherapy, definitive radiotherapy, SBRT, and proton therapy in a consecutive series of 38 patients, with postoperative morbidity and mortality as principal feasibility outcomes. ^[52]^C4 Pneumonectomy may be considered only in exceptional cases because salvage pneumonectomy after high-dose CRT is associated with substantial operative risk; its justification requires stringent selection at experienced centers. ^[49]^B3b

The expanding use of immunotherapy and targeted therapy creates additional conversion or salvage scenarios. A multicenter retrospective study evaluated salvage surgery after immune checkpoint inhibitor therapy, including conversion surgery for initially unresectable disease and true salvage surgery for local recurrence or residual disease, with perioperative outcomes and survival as endpoints. ^[44]^C4 In ALK-rearranged NSCLC, a multicenter series described 10 treatment-naive patients who received first-line alectinib and subsequently underwent anatomically planned resection after multidisciplinary discussion. ^[47]^C4

Systemic therapy and non-thoracic considerations

Systemic treatment is generally required when recurrence is polyrecurrent, metastatic, or unsuitable for definitive local therapy. Docetaxel plus ramucirumab remains a salvage option after progression on platinum chemotherapy, immune checkpoint blockade, and targeted therapy; a phase 2 study evaluated adding pembrolizumab to docetaxel and ramucirumab in recurrent or metastatic NSCLC after these prior treatments. ^[120] In EGFR-mutated stage IV disease, concurrent first-line EGFR-TKI and thoracic radiotherapy produced durable control of the primary lung lesion, but grade >3 radiation pneumonitis occurred in 20%, underscoring the need for caution when combining systemic therapy and thoracic irradiation. ^[121] Evidence from spinal SBRT reirradiation concerns previously irradiated spinal metastases and should not be extrapolated directly to thoracic locoregional recurrence. ^[45]^B3b Salvage chemotherapy data from recurrent/metastatic head and neck cancer after immune checkpoint inhibitors are not directly applicable to NSCLC and should not guide thoracic recurrence management. ^[53]^C4

Potential salvage approaches

Clinical situation	Potential approach	Key evidence or limitation
Small isolated lung recurrence	SABR	Prospective study treated lesions ≤3 cm with 50 Gy in 4 fractions. ^[122]
Isolated recurrence in or near a prior radiation field	Proton or other definitive thoracic reirradiation	Requires composite dose assessment and strict organ-at-risk constraints. ^[40]^A1c^[55]^C4
Recurrence after prior nonsurgical definitive therapy	Salvage pulmonary resection	Feasible in selected patients after multidisciplinary review; pneumonectomy is particularly high risk. ^[49]^B3b^[52]^C4
Oligorecurrent disease after CRT and durvalumab	Local therapy with or without systemic salvage	Real-world outcomes were evaluated using an oligorecurrence definition of ≤3 lesions. ^[41]^B2b
Polyrecurrent or metastatic progression	Systemic therapy	Docetaxel/ramucirumab-based salvage, including study of pembrolizumab combination, is relevant after prior platinum and immune checkpoint therapy. ^[120]

Distant Metastatic Disease

▸For advanced EGFR-mutated NSCLC, AENEAS2 evaluated first-line aumolertinib plus platinum chemotherapy versus aumolertinib alone [65].
▸Amivantamab is identified as the current standard targeted therapy for advanced EGFR exon 20 insertion NSCLC, with real-world data from 119 Italian patients [167].
▸An updated meta-analysis included 9 randomized trials and 3,443 patients evaluating PD-1/PD-L1 inhibitor plus chemotherapy versus chemotherapy alone in driver-gene-negative nonsquamous NSCLC [159].
▸Brain metastasis management evidence includes a real-world comparison of stereotactic versus whole-brain radiotherapy combined with immunotherapy and development of the BLIP prognostic score [163][168].
▸EGFR-mutated NSCLC with leptomeningeal metastasis had a reported median overall survival of 16.2 months in a 288-patient real-world cohort [164].
▸Focused ultrasound ablation combined sequentially with immune checkpoint inhibition remains investigational for liver metastases because supporting evidence consists of only 10 patients in a single-arm study [169].

Dx Diagnostic Essentials: Before selecting systemic therapy for metastatic NSCLC, establish actionable genomic status, including EGFR alterations, and characterize intracranial and extracranial disease because the cited evidence supports different strategies for driver-positive, driver-negative, brain, leptomeningeal, bone, and liver metastases [159][163][164][167][172].

! Warning: Most organ-specific evidence cited here is retrospective, prognostic, or feasibility-based; nomograms, beta-blocker associations, and focused-ultrasound results should not be treated as proof of therapeutic benefit [158][163][164][168][169][172].

Clinical scope and assessment

Distant metastatic NSCLC includes disease involving organs such as the brain, leptomeninges, liver, bone, and other extrathoracic sites; management should be individualized according to actionable genomic alterations, PD-L1 status, metastatic distribution, symptoms, performance status, and the need for local treatment. The cited evidence is heterogeneous and includes randomized trials, systematic reviews, real-world cohorts, and small feasibility studies, so treatment selection should not rely on any single retrospective prognostic model ^[155]^[156]^[157]^[159]^[163]^[164]^[168]^[169]^C.

Systemic therapy according to molecular subtype

For advanced NSCLC with EGFR-sensitive mutations, third-generation EGFR tyrosine-kinase inhibitors remain the established first-line treatment class, although acquired resistance commonly limits durability ^[65]^A1b. The phase III AENEAS2 trial directly evaluated first-line aumolertinib plus platinum-based chemotherapy versus aumolertinib monotherapy in locally advanced or metastatic EGFR-mutated NSCLC, reflecting an evidence-based strategy for intensifying initial treatment in this population ^[65]^A1b.

EGFR exon 20 insertion disease has a distinct therapeutic pathway. Amivantamab is described as the current standard targeted therapy for advanced EGFR exon 20 insertion NSCLC, and the Italian ATLAS Registry provided multicenter real-world data from 119 patients treated during 2024 ^[167]. The registry was designed to characterize treatment effectiveness, clinical features, and safety outside clinical trials; interpretation should account for its retrospective observational design ^[167].

After EGFR-TKI failure, atezolizumab, bevacizumab, carboplatin, and paclitaxel (ABCP) has demonstrated activity in EGFR-mutated NSCLC, while real-world evidence in the osimertinib era remains limited ^[171]^C. A two-institution retrospective study evaluated ABCP after EGFR-TKI failure through March 2025, including progression-free survival, overall survival, response, safety, and prognostic factors; these data support consideration of ABCP in selected post-TKI patients but do not establish it as preferable to all other subsequent therapies ^[171]^C.

For driver-gene-negative advanced nonsquamous NSCLC, an updated systematic review and meta-analysis identified 9 randomized controlled trials involving 3,443 patients comparing PD-1/PD-L1 inhibitor–plus-chemotherapy regimens with chemotherapy alone ^[159]. The analysis specifically addressed first-line efficacy and safety, supporting chemoimmunotherapy as a central systemic-treatment approach when no actionable driver alteration directs targeted therapy ^[159]. Evidence is also emerging for uncommon histologies: a systematic review and independent multicenter real-world cohort evaluated first-line immunotherapy plus chemotherapy versus chemotherapy alone in advanced pulmonary lymphoepithelioma-like carcinoma, a rare subtype characterized by regional clustering and frequent high PD-L1 expression ^[155]. In SMARCA4-deficient NSCLC, a real-world cohort compared chemoimmunotherapy alone with chemoimmunotherapy combined with antiangiogenic therapy because SMARCA4 loss may produce an immune-desert microenvironment and potential resistance to immune checkpoint inhibition ^[156].

Brain and leptomeningeal metastases

Brain metastases are common and prognostically unfavorable in NSCLC ^[163]^[168]. In driver-gene-negative NSCLC with brain metastases, a real-world inverse-probability-of-treatment-weighted analysis compared stereotactic radiotherapy plus immunotherapy with whole-brain radiotherapy plus immunotherapy; its retrospective, single-center design means that treatment choice remains dependent on intracranial disease burden, lesion number and size, symptoms, extracranial disease, and patient priorities ^[163]. The Brain-Lung Immunotherapy Prognostic (BLIP) score was developed in 1,844 NSCLC patients with brain metastases treated with immune checkpoint inhibitors and underwent internal and external validation, providing a potential prognostic framework rather than a treatment-selection substitute ^[168].

Leptomeningeal metastasis in EGFR-mutated NSCLC remains particularly difficult to treat. A real-world cohort of 288 EGFR-mutated patients with leptomeningeal metastasis reported a median overall survival of 16.2 months and developed a nomogram using LASSO selection, multivariable Cox modeling, bootstrap validation, time-dependent area under the curve, calibration, and decision-curve analyses ^[164]. The model is prognostic and should not be interpreted as proof that any specific systemic or intrathecal regimen improves survival ^[164].

Organ-directed and supportive strategies

For EGFR-mutated NSCLC with bone metastases, a retrospective observational study evaluated predictors of response and progression-free survival during icotinib therapy and developed a nomogram using LASSO regression, multivariable Cox analysis, ROC assessment, and decision-curve analysis ^[172]. These findings may assist risk stratification but require external validation before routine treatment decisions are based on the model ^[172].

A small single-arm feasibility study investigated focused ultrasound ablation surgery sequentially with immune checkpoint inhibition in 10 patients with driver-gene wild-type NSCLC and liver metastases; camrelizumab was used in 7 patients, pembrolizumab in 3, and serplulimab was used for immune rechallenge in 1 patient ^[169]^C. All participants had stable reported tolerability and safety, but the sample size and noncomparative design preclude conclusions regarding survival benefit or superiority over standard systemic and local therapies ^[169]^C.

Potential treatment modifiers remain investigational. A prospective study of 117 patients assessed germline whole-exome sequencing and machine-learning risk scores for predicting immunotherapy outcomes in advanced NSCLC because PD-L1 expression and tumor mutational burden have limited predictive accuracy in some patients ^[157]. A systematic review and meta-analysis also examined whether concomitant beta-blocker use was associated with improved outcomes in cancer patients receiving radiotherapy, but this evidence should not be used to prescribe beta-blockers solely as anticancer radiosensitizers ^[158].

Selected evidence relevant to distant metastatic NSCLC

Clinical setting	Evidence and interpretation
EGFR-sensitive advanced NSCLC	Phase III AENEAS2 evaluated aumolertinib plus platinum chemotherapy versus aumolertinib alone as first-line treatment ^[65]^A1b.
EGFR exon 20 insertion NSCLC	Amivantamab is described as the current standard; the ATLAS Registry included 119 real-world patients ^[167].
Driver-gene-negative nonsquamous NSCLC	Nine RCTs involving 3,443 patients were included in an updated systematic review of PD-1/PD-L1 inhibitor plus chemotherapy ^[159].
Brain metastases	Retrospective evidence compared stereotactic radiotherapy plus immunotherapy with whole-brain radiotherapy plus immunotherapy; the BLIP score provides prognostic stratification ^[163]^[168].
EGFR-mutated leptomeningeal metastasis	A 288-patient cohort reported median overall survival of 16.2 months and developed a prognostic nomogram ^[164].
Liver metastases	A 10-patient feasibility study evaluated focused ultrasound ablation sequentially with immune checkpoint inhibition ^[169]^C.

Oligometastatic Disease

▸Use metastasis-directed radiotherapy selectively within a multidisciplinary strategy; definitions vary from fewer than 5 bone metastases to ≤5 total metastatic lesions [81][94][129].
▸Early local treatment in solitary distant metastasis was associated with delayed multiple-metastasis development, but evidence remains observational [124].
▸SBRT may be integrated with targeted therapy or immunotherapy, although current studies are largely non-comparative or exploratory [81][86][127][149][150].
▸Thoracic radiotherapy combined with EGFR-TKIs carries substantial pneumonitis risk, including a pooled grade 3–5 incidence of 5.33% [123].
▸Central and ultra-central anatomy, motion management, tracking method, and proximity to organs at risk are critical determinants of safety [92][95][128][131].

CP Clinical Pearl: For carefully selected patients with limited metastatic burden, local therapy is best considered after integrating metastatic distribution, molecular subtype, systemic-treatment response, expected quality-of-life benefit, and technical safety.

! Warning: Do not extrapolate early-stage SBRT evidence directly to OMD, and do not assume that results from single-arm SBRT–immunotherapy studies establish a benefit over systemic therapy alone [87][91][127][150].

Definition and treatment framework

Oligometastatic disease (OMD) in NSCLC represents a limited metastatic state in which metastasis-directed local therapy may be considered alongside systemic treatment. The available 2026 evidence supports multidisciplinary selection based on metastatic burden, disease biology, anatomic feasibility, response to systemic therapy, and the patient’s ability to tolerate definitive local treatment ^[124]^[129]. The cited studies use heterogeneous definitions, including ≤5 metastatic lesions in treatment-naïve EGFR-mutant disease ^[81]^B2b, fewer than 5 bone metastases in a European SBRT cohort ^[94]^B2b, and “genuine” versus “induced” OMD classifications in a retrospective consolidative-radiotherapy study ^[129]. Consequently, outcomes should not be generalized across all oligometastatic presentations ^[127]^[129].

Local consolidative and metastasis-directed radiotherapy

Consolidative hypofractionated radiotherapy remains an established real-world strategy after systemic treatment or in selected patients with limited metastatic disease. In a retrospective cohort of 216 patients with oligometastatic NSCLC treated between 2013 and 2024, consolidative radiotherapy was delivered in fewer than 10 fractions with a biologically effective dose of ≥50 Gy; reported endpoints included local control, progression-free survival, overall survival, and toxicity ^[129]. The study specifically evaluated both “genuine” and “induced” OMD, addressing the real-world distinction between limited disease present at diagnosis and disease rendered limited after systemic therapy ^[129].

For solitary distant metastasis, a multicenter retrospective cohort of 139 patients found that driver-gene status, tumor stage, systemic therapy, and local treatment were associated with progression-free survival ^[124]. Importantly, early local treatment was associated with delayed development of multiple metastases, with a reported hazard ratio of 0.55 and a 95% confidence interval beginning at 0. ^[124] Because this was an observational study, the association should not be interpreted as proof that treatment timing independently improves survival ^[124].

Bone oligometastases are a clinically relevant OMD subgroup. A 15-center European retrospective study evaluated 85 patients with 111 bone metastases, each patient receiving SBRT for fewer than 5 bone metastases; outcomes included freedom from local recurrence, progression-free survival, overall survival, and adverse events, with a median follow-up of 14 months ^[94]^B2b. These data support SBRT as a potential local treatment for selected bone-limited disease, while the retrospective design and relatively short follow-up limit certainty regarding long-term benefit ^[94]^B2b.

Patient-reported outcomes are also important when applying metastasis-directed SBRT. The prospective ESTRO/EORTC OligoCare cohort included patients with breast, colorectal, NSCLC, and prostate OMD and assessed health-related quality of life at baseline and after SBRT ^[93]^B2b. The cohort was designed to characterize short-term quality-of-life change and factors associated with baseline status and its evolution, providing complementary evidence to tumor-control endpoints ^[93]^B2b.

Integration with systemic therapy and immunotherapy

The ABLATE phase II multicenter randomized, non-comparative study evaluated treatment-naïve patients with activating EGFR mutations, specifically exon 19 deletion or L858R, and synchronous OMD defined by ≤5 metastatic lesions. Patients received lazertinib alone or lazertinib combined with SBRT; the study was designed to evaluate clinical efficacy and safety of this treatment strategy ^[81]^B2b. These findings are most directly applicable to molecularly selected EGFR-mutant patients and should not be extrapolated to oncogene-negative disease without supporting evidence ^[81]^B2b.

In previously treated advanced NSCLC, a multicenter single-arm phase II study enrolled 83 patients after progression on at least one standard systemic-therapy line and combined SBRT with nivolumab. SBRT was directed to the primary lung lesion or, when no visible primary remained, to an involved nodal lesion; an exploratory analysis examined bone metastases ^[150]. The single-arm design prevents separation of the effects of SBRT from those of nivolumab or patient selection ^[150].

The SKYROCKET phase II study evaluated SBRT to all metastatic sites followed within 7 days by atezolizumab plus tiragolumab in treatment-naïve, PD-L1-positive advanced NSCLC; progression-free survival from SBRT was the primary endpoint, with exploratory single-cell RNA sequencing analyses ^[86]^B2b. This remains hypothesis-generating because it was single-center, single-arm, and restricted to a biomarker-selected population ^[86]^B2b. A separate prospective exploratory case series examined sequential SBRT and tislelizumab after four cycles of platinum-doublet chemotherapy in a small, preselected cohort of advanced non-squamous NSCLC without specified driver mutations; it was explicitly designed to generate hypotheses rather than definitive efficacy conclusions ^[149]^C.

A systematic review of SBRT combined with immune checkpoint inhibitors found substantial heterogeneity in treatment timing, dose, fractionation, study design, and toxicity reporting; therefore, an optimal sequencing strategy cannot be established from the available evidence ^[127]. Radiation pneumonitis is a particular concern when thoracic radiotherapy is combined with EGFR-TKIs. A meta-analysis of 20 studies involving 693 patients with unresectable stage III/IV NSCLC reported a pooled overall pneumonitis incidence of 62.06%, grade 1–2 incidence of 52.09%, and grade 3–5 incidence of 5.33% ^[123]. These estimates mainly concern thoracic irradiation with EGFR-TKIs and should not be assumed to represent the risk from every metastasis-directed SBRT regimen ^[123].

Technical selection and safety

SBRT planning is particularly challenging for central and ultra-central lesions because of nearby mediastinal organs at risk. Updated systematic-review evidence specifically evaluated local control, overall survival, dose prescriptions, and adverse effects for ultra-central lung malignancies, but the safety and efficacy of this approach remain dependent on anatomy and treatment technique ^[92]^B2a. Contemporary real-world data likewise emphasize the limited prospective evidence for central and ultra-central tumors ^[95]^C4.

Proton-based hypofractionated or stereotactic radiotherapy is being evaluated for high-risk lung tumors. A prospective multi-institutional registry included adults treated in ≤15 fractions, using either 4–5 fractions at ≥10 Gy per fraction and ≥48 Gy total, or 8–15 fractions at ≥3.5 Gy per fraction and ≥52.5 Gy total; local control was analyzed with death as a competing risk ^[148]. These data concern lung tumors broadly and do not establish proton therapy as superior for oligometastatic NSCLC ^[148]. Fiducial-marker insertion may facilitate real-time tracking for peripheral pulmonary lesions or intrathoracic oligometastases, but approaches differ in tracking performance and complications, including pneumothorax ^[128]. Dosimetric simulation data also show that tumor-based and fiducial-based tracking can produce different robustness profiles in lung SBRT, underscoring the need for motion assessment and image-guided quality assurance ^[131].

Evidence boundaries

Evidence directly addressing OMD is dominated by retrospective cohorts, single-arm studies, exploratory series, and heterogeneous systematic reviews ^[93]^B2b^[94]^B2b^[123]^[127]^[129]. Studies of SBRT for medically inoperable stage I disease, including Bayesian reanalysis of LUSTRE, concern localized primary tumors rather than metastatic disease and should not be used as direct evidence for OMD ^[87]^A1b. Similarly, comparisons of sublobar resection, SBRT, and thermal ablation address early-stage NSCLC in patients unable to tolerate lobectomy, not metastatic NSCLC ^[91]^B2a. Long-term SBRT follow-up studies in stage I disease and radiomics models for occult nodal metastasis also inform local-treatment practice but do not establish management of OMD ^[125]^[151]^C. Neoadjuvant immunotherapy plus chemotherapy in resectable EGFR-mutant stage II–IIIB NSCLC is likewise outside the oligometastatic setting ^[126].

Selected evidence relevant to oligometastatic NSCLC

Clinical context	Evidence	Main limitation
Solitary distant metastasis	139-patient multicenter retrospective cohort; early local treatment associated with delayed multiple metastases, HR 0.55 ^[124]	Nonrandomized design
Bone OMD	85 patients; 111 bone metastases; SBRT for <5 bone metastases ^[94]^B2b	Retrospective cohort; median follow-up 14 months
Consolidative radiotherapy	216-patient real-world cohort; BED ≥50 Gy in <10 fractions ^[129]	Retrospective; heterogeneous genuine and induced OMD
EGFR-mutant synchronous OMD	ABLATE evaluated lazertinib with or without SBRT for ≤5 lesions ^[81]^B2b	Randomized but non-comparative phase II design
SBRT plus immunotherapy	Studies evaluated nivolumab, atezolizumab/tiragolumab, or tislelizumab combinations ^[86]^B2b^[149]^C^[150]	Single-arm or exploratory studies
EGFR-TKI plus thoracic RT	Pooled pneumonitis: 62.06% overall, 5.33% grade 3–5 ^[123]	Mixed regimens and disease stages

Prognosis of Recurrent Disease

▸Postoperative recurrence remains clinically important, with an approximate **30% 5-year recurrence rate** reported in an early-stage cohort. [138]
▸Postoperative recurrence may occur after a prolonged disease-free interval; the median interval was **511 days** in a contemporary recurrent-NSCLC cohort. [107]
▸Distant metastases were present in 169 of 229 patients with postoperative recurrence in that cohort. [107]
▸Idiopathic pulmonary fibrosis was associated with markedly inferior **5-year recurrence-free probability: 32.3% versus 76.1%** without IPF. [145]
▸Recurrence risk models increasingly incorporate pathological features, PET activity, molecular alterations, proteomics, methylation, CT imaging, and artificial intelligence, but many models lack prospective clinical validation. [32,35,112,140,141]
▸Adjuvant targeted therapy is altering recurrence expectations in ALK- and RET-altered disease; the supplied trial abstracts for ensartinib and selpercatinib do not provide numerical efficacy results. [15,135,139]

CP Clinical Pearl: Prognosis after recurrence is not determined by recurrence alone: recurrence site, molecular profile, time from surgery, prior adjuvant treatment, and feasibility of local therapy should be assessed together. [107,137]

! Warning: Most evidence for salvage surgery, AI prediction, molecular signatures, methylation assays, and transplantation is retrospective, selected, or exploratory; these findings should not be interpreted as broadly applicable treatment standards. [32,35,44,140,142]

Overall recurrence risk and prognostic framework

Recurrence remains a substantial problem after apparently curative treatment of early-stage NSCLC; one contemporary proteomic study describes an approximate 30% 5-year recurrence rate after complete resection. ^[138] Prognosis after recurrence should therefore be interpreted in the context of pathological stage, resection completeness, recurrence pattern, molecular subtype, interval from definitive treatment, prior systemic therapy, and the feasibility of local treatment. ^[107]^B3b^[137]^[153]

In a multicenter cohort of 229 patients with postoperative recurrent NSCLC, the median interval from surgery to recurrence was 511 days; 169 patients developed distant metastases, indicating that recurrence frequently presents as systemic rather than purely locoregional disease. ^[107]^B3b Among these patients, biomarker testing and multigene testing were clinically relevant to treatment selection, although the abstract does not provide complete outcome estimates by biomarker subgroup. ^[107]^B3b

Pathological, clinical, and host factors

EGFR mutation status has been specifically evaluated in resected stage I–III disease in an updated systematic review and meta-analysis of 20 studies. ^[136] The analysis examined pooled recurrence rates, recurrence risk ratios, and disease-free-survival hazard ratios according to stage, recurrence site, mutation subtype, and adjuvant treatment; the available abstract does not report the pooled numerical estimates, so EGFR status should be regarded as an important prognostic and treatment-stratification variable without assigning a quantitative recurrence risk from this source. ^[136]

Idiopathic pulmonary fibrosis is associated with particularly unfavorable postoperative outcomes. ^[145] In a cohort of 437 patients with pathological stage I NSCLC who underwent complete resection and systematic nodal dissection, propensity-matched 5-year recurrence-free probability was 32.3% with IPF versus 76.1% without IPF (P<0.001), and IPF was investigated as a predictor of local recurrence. ^[145]

High metabolic activity and occult pathological upstaging may also identify patients at increased risk. ^[112]^C In patients clinically staged as IA (T1N0M0), preoperative PET maximum standardized uptake value was evaluated in relation to pathological upstaging and recurrence-free survival, although the available abstract does not provide the final effect estimates. ^[112]^C In stage IA disease, a high-risk recurrence phenotype defined by spread through air spaces, lymphovascular invasion, a predominant solid, micropapillary, or complex glandular pattern, or a >5% solid/micropapillary component was the target of a multicenter multimodal prediction model. ^[141]

Response to neoadjuvant treatment and definitive local therapy

Major pathological response after neoadjuvant chemoimmunotherapy is prognostically heterogeneous. ^[152] In a dual-center retrospective cohort of 588 resectable NSCLC patients treated with neoadjuvant chemoimmunotherapy followed by radical surgery, patients were categorized according to pathological complete response and non-complete-response major pathological response, with recurrence-free survival and recurrence patterns as endpoints. ^[152] The study specifically challenges the assumption that all major pathological responses have equivalent prognosis; the abstract does not provide the comparative numerical RFS estimates. ^[152]

For stage II–III disease treated with induction immunochemotherapy, a 12-center pragmatic cohort compared definitive surgery with definitive radiotherapy using propensity-score matching and assessed progression-free survival, overall survival, and recurrence patterns. ^[137] Because this was a retrospective comparison, treatment selection and residual confounding remain relevant when interpreting prognosis. ^[137] In selected cT4N0–2bM0 patients who achieved R0 resection, a multicenter retrospective study evaluated relapse-free survival and overall survival according to T4 subgroup and clinical nodal category, providing outcome data relevant to surgical selection in locally advanced disease. ^[153]

Salvage surgery after immune-checkpoint-inhibitor treatment has also been examined. ^[44]^C4 The Japanese CReGYT-05 multicenter retrospective study included patients undergoing conversion surgery for initially unresectable disease or true salvage surgery for local recurrence or residual disease after immunotherapy, and assessed perioperative outcomes, overall survival, and recurrence-related outcomes. ^[44]^C4 Such surgery represents a highly selected strategy and should not be generalized to all patients with recurrent disease. ^[44]^C4

Molecularly directed adjuvant therapy and recurrence prevention

Adjuvant targeted therapy is changing the expected prognosis for molecularly defined early-stage disease. ^[139] Alectinib was reported to reduce the risk of recurrence or death by 76% in ALK-positive NSCLC and was modeled against platinum chemotherapy for stage IB tumors ≥4 cm through stage IIIA disease using locoregional and metastatic recurrence states over 10 years. ^[139] A phase 3 trial randomized 274 patients with completely resected ALK-positive stage IB–IIIB NSCLC after adjuvant chemotherapy to 24 months of ensartinib or placebo; the primary endpoint was disease-free survival in stage II–IIIB disease, but the supplied abstract does not report the trial’s numerical results. ^[15]^A1b

A separate phase 3 trial evaluated up to 3 years of adjuvant selpercatinib versus placebo after definitive therapy for RET fusion-positive NSCLC, with event-free survival as the primary endpoint in stage II–IIIA disease. ^[135] Selpercatinib is described as a potent, selective, central-nervous-system-penetrant RET inhibitor, but the supplied abstract does not provide comparative event-free-survival or overall-survival estimates. ^[135]

Recurrence prediction and emerging biomarkers

Artificial-intelligence prediction models may improve postoperative risk stratification. ^[32]^B2a A systematic review identified 17 original studies from 2,672 records; random-forest and random-survival-forest approaches were among the evaluated methods, and model performance varied according to data modality and validation strategy. ^[32]^B2a Multimodal models integrating biopsy whole-slide imaging, CT morphology, and clinical variables have been developed for stage IA disease, including a three-center study of 342 patients designed to predict a high-risk recurrence phenotype associated with poor disease-free survival. ^[141]

Proteomic profiling is another emerging approach. ^[138] A discovery cohort of 351 patients with stage I NSCLC and an external prospective validation cohort of 103 patients were used to develop and validate a protein signature integrated with clinical features for postoperative recurrence prediction. ^[138] Molecular-based prediction models overall remain heterogeneous in design and evidence quality; a systematic review and meta-analysis evaluated models predicting recurrence-free, cancer-specific, or overall survival after curative treatment, but the supplied abstract does not provide pooled discrimination estimates. ^[140]^C

Additional investigational markers include RASSF1A and SHOX2 methylation in intraoperative pleural-lavage fluid, which was evaluated for microdissemination and postoperative prognosis in a prospective cohort of 43 patients who did not receive adjuvant chemotherapy. ^[35]^B2b These assays remain prognostic or investigational and should not replace established pathological staging and molecular testing. ^[35]^B2b^[140]^C

Special populations and unusual strategies

Young patients may have clinically important early and brain recurrence risk. ^[146] A multicenter study included 224 patients younger than 50 years after anatomical resection and evaluated early recurrence within 12 months, brain metastasis, recurrence-free survival, and overall survival using inflammatory and pathological variables. ^[146]

In medically refractory, lung-limited stage IV NSCLC, lung transplantation has been prospectively evaluated as an exceptional strategy. ^[142] Among 98 eligible adults, 17 underwent transplantation and 81 did not because of ineligibility or nonreceipt; the registry compared survival with medical management alone. ^[142] This evidence is limited by single-center design, selection, and small transplant numbers, and it should not be considered standard management for recurrent metastatic NSCLC. ^[142]

Selected prognostic factors and evidence

Factor or intervention	Prognostic implication	Evidence
Complete resection of early-stage NSCLC	Recurrence remains possible; approximately 30% 5-year recurrence was reported in one cohort	^[138]
Idiopathic pulmonary fibrosis	5-year recurrence-free probability 32.3% vs 76.1% without IPF	^[145]
Postoperative recurrence pattern	Distant metastases occurred in 169/229 patients in one recurrent-disease cohort	^[107]^B3b
ALK-directed adjuvant therapy	Alectinib was reported to reduce recurrence or death by 76%; ensartinib phase 3 DFS results were not provided in the supplied abstract	^[15]^A1b^[139]
RET-directed adjuvant therapy	Selpercatinib was studied for up to 3 years; comparative event-free-survival results were not provided in the supplied abstract	^[135]
High-risk pathological phenotype	STAS, LVI, solid/micropapillary or complex glandular patterns, and a >5% solid/micropapillary component define a high-risk phenotype in one model	^[141]

References

[1]
Ettinger DS, Wood DE, Aisner DL et al.. “Non-Small Cell Lung Cancer, Version 3.2022, NCCN Clinical Practice Guidelines in Oncology.” Journal of the National Comprehensive Cancer Network : JNCCN (2022). PMID: 35545176 ↗
L1GUIDELINECited in: Patterns of Recurrence, Workup of Suspected Recurrence
[2]
Yan TD, Black D, Bannon PG et al.. “Systematic review and meta-analysis of randomized and nonrandomized trials on safety and efficacy of video-assisted thoracic surgery lobectomy for early-stage non-small-cell lung cancer.” Journal of clinical oncology : official journal of the American Society of Clinical Oncology (2009). PMID: 19289625 ↗
L1SR_MA_RCTCited in: Patterns of Recurrence
[3]
Sugawara S, Lee JS, Kang JH et al.. “Nivolumab with carboplatin, paclitaxel, and bevacizumab for first-line treatment of advanced nonsquamous non-small-cell lung cancer.” Annals of oncology : official journal of the European Society for Medical Oncology (2021). PMID: 34139272 ↗
L1RCTCited in: Patterns of Recurrence
[4]
Tanvetyanon T, Robinson LA, Schell MJ et al.. “Outcomes of adrenalectomy for isolated synchronous versus metachronous adrenal metastases in non-small-cell lung cancer: a systematic review and pooled analysis.” Journal of clinical oncology : official journal of the American Society of Clinical Oncology (2008). PMID: 18309950 ↗
L2SR_COHORTCited in: Patterns of Recurrence
[5]
Brahmer JR, Lee JS, Ciuleanu TE et al.. “Five-Year Survival Outcomes With Nivolumab Plus Ipilimumab Versus Chemotherapy as First-Line Treatment for Metastatic Non-Small-Cell Lung Cancer in CheckMate 227.” Journal of clinical oncology : official journal of the American Society of Clinical Oncology (2022). PMID: 36223558 ↗
L1RCTCited in: Patterns of Recurrence
[6]
Jänne PA, Planchard D, Kobayashi K et al.. “CNS Efficacy of Osimertinib With or Without Chemotherapy in Epidermal Growth Factor Receptor-Mutated Advanced Non-Small-Cell Lung Cancer.” Journal of clinical oncology : official journal of the American Society of Clinical Oncology (2023). PMID: 38042525 ↗
L1RCTCited in: Patterns of Recurrence, Distant Metastatic Disease
[7]
Zhang Y, Qian B, Song Q et al.. “Phase III Study of Mediastinal Lymph Node Dissection for Ground Glass Opacity-Dominant Lung Adenocarcinoma.” Journal of clinical oncology : official journal of the American Society of Clinical Oncology (2025). PMID: 40690727 ↗
L1RCTCited in: Patterns of Recurrence
[8]
Besse B, Mazières J, Ribassin-Majed L et al.. “Pazopanib or placebo in completely resected stage I NSCLC patients: results of the phase II IFCT-0703 trial.” Annals of oncology : official journal of the European Society for Medical Oncology (2017). PMID: 28327934 ↗
L2RCT_PHASE2Cited in: Patterns of Recurrence, Prognosis of Recurrent Disease
[9]
Allignet B, De Ruysscher D, Martel-Lafay I et al.. “Stereotactic body radiation therapy in unresectable stage III non-small cell lung cancer: A systematic review.” Cancer treatment reviews (2023). PMID: 37210766 ↗
L4SR_COHORTCited in: Patterns of Recurrence, Oligometastatic Disease
[10]
Wink KCJ, van Baardwijk A, Troost EGC et al.. “Nodal recurrence after stereotactic body radiotherapy for early stage non-small cell lung cancer: Incidence and proposed risk factors.” Cancer treatment reviews (2017). PMID: 28437679 ↗
L2SR_COHORTCited in: Patterns of Recurrence, Oligometastatic Disease
[11]
Peters S, Bexelius C, Munk V et al.. “The impact of brain metastasis on quality of life, resource utilization and survival in patients with non-small-cell lung cancer.” Cancer treatment reviews (2016). PMID: 27019457 ↗
L2SR_COHORTCited in: Patterns of Recurrence
[12]
Yoshimura A, Takeda T, Tanimura K et al.. “Impact of the Lung Immune Prognostic Index in non-small-cell lung cancer patients with PD-L1-low/negative tumors receiving chemoimmunotherapy: a real-world multicenter retrospective study.” ESMO open (2025). PMID: 41270701 ↗
L2PROSPECTIVE_COHORTCited in: Patterns of Recurrence
[13]
Ito K, Morise M, Wakuda K et al.. “A multicenter cohort study of osimertinib compared with afatinib as first-line treatment for EGFR-mutated non-small-cell lung cancer from practical dataset: CJLSG1903.” ESMO open (2021). PMID: 33984681 ↗
L2PROSPECTIVE_COHORTCited in: Patterns of Recurrence
[14]
Jamal-Hanjani M, Wilson GA, McGranahan N et al.. “Tracking the Evolution of Non-Small-Cell Lung Cancer.” The New England journal of medicine (2017). PMID: 28445112 ↗
L2PROSPECTIVE_COHORTCited in: Patterns of Recurrence
[15]
Yue D, Huang M, Song P et al.. “Ensartinib in Resected ALK-Positive Non-Small-Cell Lung Cancer.” The New England journal of medicine (2026). PMID: 42418775 ↗
L1RCTCited in: Patterns of Recurrence
[16]
Borghaei H, O'Byrne KJ, Paz-Ares L et al.. “Nivolumab plus chemotherapy in first-line metastatic non-small-cell lung cancer: results of the phase III CheckMate 227 Part 2 trial.” ESMO open (2023). PMID: 37988950 ↗
L1RCTCited in: Patterns of Recurrence
[17]
O'Byrne KJ, Lee KH, Kim SW et al.. “First-line nivolumab + ipilimumab in advanced NSCLC: CheckMate 227 subpopulation analyses in Asian patients.” ESMO open (2022). PMID: 35158207 ↗
L1RCTCited in: Patterns of Recurrence
[18]
Reck M, Ciuleanu TE, Cobo M et al.. “First-line nivolumab plus ipilimumab with two cycles of chemotherapy versus chemotherapy alone (four cycles) in advanced non-small-cell lung cancer: CheckMate 9LA 2-year update.” ESMO open (2021). PMID: 34607285 ↗
L1RCTCited in: Patterns of Recurrence
[19]
Paz-Ares L, Ciuleanu TE, Cobo M et al.. “First-line nivolumab plus ipilimumab combined with two cycles of chemotherapy in patients with non-small-cell lung cancer (CheckMate 9LA): an international, randomised, open-label, phase 3 trial.” The Lancet. Oncology (2021). PMID: 33476593 ↗
L1RCTCited in: Patterns of Recurrence, Prognosis of Recurrent Disease
[20]
Péchoux CL, Sun A, Slotman BJ et al.. “Prophylactic cranial irradiation for patients with lung cancer.” The Lancet. Oncology (2016). PMID: 27396646 ↗
L1RCTCited in: Patterns of Recurrence
[21]
Chun SG, Hu C, Choy H et al.. “Impact of Intensity-Modulated Radiation Therapy Technique for Locally Advanced Non-Small-Cell Lung Cancer: A Secondary Analysis of the NRG Oncology RTOG 0617 Randomized Clinical Trial.” Journal of clinical oncology : official journal of the American Society of Clinical Oncology (2016). PMID: 28034064 ↗
L1RCTCited in: Workup of Suspected Recurrence, Prognosis of Recurrent Disease
[22]
Madan R, El Alam RH, Walker CM et al.. “ACR Appropriateness Criteria® Lung Cancer-Surveillance After Therapy.” Journal of the American College of Radiology : JACR (2025). PMID: 40409885 ↗
L1GUIDELINECited in: Workup of Suspected Recurrence
[23]
Takada K, Takamori S, Shimokawa M et al.. “Assessment of the albumin-bilirubin grade as a prognostic factor in patients with non-small-cell lung cancer receiving anti-PD-1-based therapy.” ESMO open (2021). PMID: 34942439 ↗
L3COHORTCited in: Workup of Suspected Recurrence, Prognosis of Recurrent Disease
[24]
Senthi S, Lagerwaard FJ, Haasbeek CJ et al.. “Patterns of disease recurrence after stereotactic ablative radiotherapy for early stage non-small-cell lung cancer: a retrospective analysis.” The Lancet. Oncology (2012). PMID: 22727222 ↗
L3RETROSPECTIVE_COHORTCited in: Workup of Suspected Recurrence, Local-Regional Recurrence, Prognosis of Recurrent Disease
[25]
Loganadane G, Martinetti F, Mercier O et al.. “Stereotactic ablative radiotherapy for early stage non-small cell lung cancer: A critical literature review of predictive factors of relapse.” Cancer treatment reviews (2016). PMID: 27768919 ↗
L5NARRATIVE_REVIEWCited in: Workup of Suspected Recurrence
[26]
Xia L, Mei J, Kang R et al.. “Perioperative ctDNA-Based Molecular Residual Disease Detection for Non-Small Cell Lung Cancer: A Prospective Multicenter Cohort Study (LUNGCA-1).” Clinical cancer research : an official journal of the American Association for Cancer Research (2022). PMID: 34844976 ↗
L2PROSPECTIVE_COHORTCited in: Workup of Suspected Recurrence
[27]
Sandhu SK, Schelman WR, Wilding G et al.. “The poly(ADP-ribose) polymerase inhibitor niraparib (MK4827) in BRCA mutation carriers and patients with sporadic cancer: a phase 1 dose-escalation trial.” The Lancet. Oncology (2013). PMID: 23810788 ↗
L4PHASE_1_TRIALCited in: Workup of Suspected Recurrence
[28]
Guldbrandsen KF, Bloch M, Skougaard K et al.. “Diagnostic Accuracy of [18F]FDG PET/CT versus CT for NSCLC Surveillance: Secondary Analysis of a Randomized Clinical Trial.” Clinical lung cancer (2025). PMID: 41387040 ↗
L1RCTCited in: Workup of Suspected Recurrence
[29]
Zhang JT, Liu SY, Gao X et al.. “Follow-up Analysis Enhances Understanding of Molecular Residual Disease in Localized Non-Small Cell Lung Cancer.” Clinical cancer research : an official journal of the American Association for Cancer Research (2025). PMID: 39853318 ↗
L4COHORTCited in: Workup of Suspected Recurrence
[30]
Arcidiacono F, Anselmo P, Casale M et al.. “Five-Year Survival and Safety of SABR in Patients with Unresectable Locally Advanced Non-Small Cell Lung Cancer unfit for Concurrent Radio-chemotherapy: Focus on Patterns of Local Recurrence from the START-NEW-ERA Non-randomized Phase 2 Trial.” International journal of radiation oncology, biology, physics (2025). PMID: 40992670 ↗
L2RCT_PHASE2Cited in: Workup of Suspected Recurrence
[31]
Wu J, Zhang Y, Wang J et al.. “Accuracy of Radiomics-Based Machine Learning for Predicting Risk of Recurrence in Non-Small Cell Lung Cancer: Systematic Review and Meta-Analysis.” Journal of medical Internet research (2026). PMID: 41940422 ↗
L2SR_COHORTCited in: Workup of Suspected Recurrence
[32]
Yang Y, He H, Yu C et al.. “Artificial Intelligence Models to Predict Recurrence Risk Prediction in Early-Stage Non-Small Cell Lung Cancer: A Systematic Review.” European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery (2026). PMID: 41666303 ↗
L2SR_COHORTCited in: Workup of Suspected Recurrence
[33]
Lu D, Lin N, Li S et al.. “Predictive Effectiveness of Circulating Tumor DNA in Recurrent Early-Stage Non-Small Cell Lung Cancer: An Updated Meta-Analysis.” JCO precision oncology (2025). PMID: 41066727 ↗
L2SR_COHORTCited in: Workup of Suspected Recurrence
[34]
Lanuti M, Suh RD, Criner GJ et al.. “Systematic Review of Image-Guided Thermal Ablation for Treatment of High-Risk Patients with Stage I Non-Small Cell Lung Cancer.” Seminars in thoracic and cardiovascular surgery (2024). PMID: 39662536 ↗
L2SR_COHORTCited in: Workup of Suspected Recurrence
[35]
Hou J, Xiao J, Yang B et al.. “Value of RASSF1A and SHOX2 methylation detection in intraoperative pleural lavage fluid for potential microdissemination and prognosis evaluation in non-small cell lung cancer.” World journal of surgical oncology (2026). PMID: 42116130 ↗
L2PROSPECTIVE_COHORTCited in: Workup of Suspected Recurrence
[36]
Toth AJ, Robert SM, Fahy T et al.. “Multidisciplinary review outperforms qualitative MR perfusion in distinguishing post-radiation brain metastasis recurrence versus radionecrosis.” Journal of neuro-oncology (2025). PMID: 41219616 ↗
L2PROSPECTIVE_COHORTCited in: Workup of Suspected Recurrence
[37]
Xia L, Pu Q, Kang R et al.. “Dynamic ctDNA informs whole-course postoperative precise management of NSCLC (LUNGCA study).” Journal of the National Cancer Institute (2025). PMID: 40131728 ↗
L2PROSPECTIVE_COHORTCited in: Workup of Suspected Recurrence
[38]
. “MRD May Predict Relapse in NSCLC.” Cancer discovery (2020). PMID: 32467342 ↗
L5OTHERCited in: Workup of Suspected Recurrence
[39]
Chen K, Yang F, Shen H et al.. “Individualized tumor-informed circulating tumor DNA analysis for postoperative monitoring of non-small cell lung cancer.” Cancer cell (2023). PMID: 37683638 ↗
L5OTHERCited in: Workup of Suspected Recurrence
[40]
Simone CB, Amini A, Chetty IJ et al.. “American Radium Society Appropriate Use Criteria Systematic Review and Guidelines on Reirradiation for Non-Small Cell Lung Cancer Executive Summary.” International journal of radiation oncology, biology, physics (2025). PMID: 40185207 ↗
L1GUIDELINECited in: Local-Regional Recurrence
[41]
Ciammella P, Iori F, Borghetti P et al.. “Locally advanced NSCLC: overview of real-world pattern of recurrence in durvalumab era (LEOPARD trial).” Lung cancer (Amsterdam, Netherlands) (2025). PMID: 40876065 ↗
L2PROSPECTIVE_COHORTCited in: Local-Regional Recurrence
[42]
Munoz-Schuffenegger P, Kandel S, Alibhai Z et al.. “A Prospective Study of Magnetic Resonance Imaging Assessment of Post-radiation Changes Following Stereotactic Body Radiation Therapy for Non-small Cell Lung Cancer.” Clinical oncology (Royal College of Radiologists (Great Britain)) (2019). PMID: 31176537 ↗
L4PROSPECTIVE_COHORTCited in: Local-Regional Recurrence
[43]
Brooks ED, Sun B, Feng L et al.. “Association of Long-term Outcomes and Survival With Multidisciplinary Salvage Treatment for Local and Regional Recurrence After Stereotactic Ablative Radiotherapy for Early-Stage Lung Cancer.” JAMA network open (2018). PMID: 30646121 ↗
L2PROSPECTIVE_COHORTCited in: Local-Regional Recurrence
[44]
Tane S, Nishikubo M, Manabe T et al.. “Efficacy and Safety of Salvage Surgery After Immunotherapy in Non-small Cell Lung Cancer: A Multi-institutional Retrospective Study.” Annals of surgical oncology (2026). PMID: 41746575 ↗
L4COHORTCited in: Local-Regional Recurrence
[45]
Vuppala NK, LeCompte MC, Patel PP et al.. “Oncological outcomes and safety after spinal reirradiation with stereotactic body radiotherapy.” Journal of neurosurgery. Spine (2025). PMID: 40939207 ↗
L3COHORTCited in: Local-Regional Recurrence
[46]
Odwuor A, Lee P, Chang JY et al.. “Outcomes and Toxicity following 3 or More Definitive Courses of Thoracic Radiation Therapy for Non-Small Cell Lung Cancer.” Clinical lung cancer (2025). PMID: 40318943 ↗
L4COHORTCited in: Local-Regional Recurrence
[47]
Lococo F, Cancellieri A, Chiappetta M et al.. “Salvage Surgery After First-Line Alectinib for Locally-Advanced/Metastatic ALK-Rearranged NSCLC: Pathological Response and Perioperative Results.” Clinical lung cancer (2023). PMID: 37061413 ↗
L4COHORTCited in: Local-Regional Recurrence
[48]
Zhang J, Mao J, Xu D et al.. “Pattern of failure and clinical value of local therapy for oligo-recurrence in locally advanced non-small cell lung cancer after definitive chemoradiation: Impact of driver mutation status.” Cancer medicine (2022). PMID: 36524618 ↗
L3COHORTCited in: Local-Regional Recurrence
[49]
Joosten PJM, Dickhoff C, van der Noort V et al.. “Is pneumonectomy justifiable for patients with a locoregional recurrence or persistent disease after curative intent chemoradiotherapy for locally advanced non-small cell lung cancer?” Lung cancer (Amsterdam, Netherlands) (2020). PMID: 33220611 ↗
L3COHORTCited in: Local-Regional Recurrence
[50]
Muller DA, Dutta SW, Aliotta E et al.. “Clinical Outcomes and Predictors of Lung Toxicity After Multiple Courses of Lung Stereotactic Body Radiotherapy for Early-Stage Non-Small Cell Lung Cancer.” Clinical lung cancer (2020). PMID: 32690439 ↗
L4COHORTCited in: Local-Regional Recurrence
[51]
Kowalchuk RO, Waters MR, Richardson KM et al.. “Stereotactic Body Radiation Therapy for Salvage Treatment of Recurrent Non-Small Cell Lung Cancer.” Practical radiation oncology (2020). PMID: 32454175 ↗
L4COHORTCited in: Local-Regional Recurrence
[52]
Kobayashi AK, Horinouchi H, Nakayama Y et al.. “Salvage surgery after chemotherapy and/or radiotherapy including SBRT and proton therapy: A consecutive analysis of 38 patients.” Lung cancer (Amsterdam, Netherlands) (2020). PMID: 32422344 ↗
L4COHORTCited in: Local-Regional Recurrence
[53]
Saleh K, Daste A, Martin N et al.. “Response to salvage chemotherapy after progression on immune checkpoint inhibitors in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck.” European journal of cancer (Oxford, England : 1990) (2019). PMID: 31574417 ↗
L4COHORTCited in: Local-Regional Recurrence
[54]
Grass GD, Naghavi AO, Abuodeh YA et al.. “Analysis of Relapse Events After Definitive Chemoradiotherapy in Locally Advanced Non-Small-Cell Lung Cancer Patients.” Clinical lung cancer (2018). PMID: 30268836 ↗
L3COHORTCited in: Local-Regional Recurrence
[55]
Chao HH, Berman AT, Simone CB et al.. “Multi-Institutional Prospective Study of Reirradiation with Proton Beam Radiotherapy for Locoregionally Recurrent Non-Small Cell Lung Cancer.” Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer (2016). PMID: 27826034 ↗
L4COHORTCited in: Local-Regional Recurrence
[56]
Dickhoff C, Dahele M, Paul MA et al.. “Salvage surgery for locoregional recurrence or persistent tumor after high dose chemoradiotherapy for locally advanced non-small cell lung cancer.” Lung cancer (Amsterdam, Netherlands) (2016). PMID: 26973215 ↗
L4COHORTCited in: Local-Regional Recurrence
[57]
Binkley MS, Hiniker SM, Chaudhuri A et al.. “Dosimetric Factors and Toxicity in Highly Conformal Thoracic Reirradiation.” International journal of radiation oncology, biology, physics (2015). PMID: 26831903 ↗
L4COHORTCited in: Local-Regional Recurrence
[58]
Mizobuchi T, Yamamoto N, Nakajima M et al.. “Salvage surgery for local recurrence after carbon ion radiotherapy for patients with lung cancer.” European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery (2015). PMID: 26468271 ↗
L3COHORTCited in: Local-Regional Recurrence
[59]
Liao Z, Lee JJ, Komaki R et al.. “Bayesian Adaptive Randomization Trial of Passive Scattering Proton Therapy and Intensity-Modulated Photon Radiotherapy for Locally Advanced Non-Small-Cell Lung Cancer.” Journal of clinical oncology : official journal of the American Society of Clinical Oncology (2018). PMID: 29293386 ↗
L1RCTCited in: Distant Metastatic Disease
[60]
Scagliotti GV, Krzakowski M, Szczesna A et al.. “Sunitinib plus erlotinib versus placebo plus erlotinib in patients with previously treated advanced non-small-cell lung cancer: a phase III trial.” Journal of clinical oncology : official journal of the American Society of Clinical Oncology (2012). PMID: 22564989 ↗
L1RCTCited in: Distant Metastatic Disease
[61]
Kurup A, Lin C-, Murry DJ et al.. “Recombinant human angiostatin (rhAngiostatin) in combination with paclitaxel and carboplatin in patients with advanced non-small-cell lung cancer: a phase II study from Indiana University.” Annals of oncology : official journal of the European Society for Medical Oncology (2005). PMID: 16282244 ↗
L2RCT_PHASE2Cited in: Distant Metastatic Disease
[62]
Yang JT, Wijetunga NA, Pentsova E et al.. “Randomized Phase II Trial of Proton Craniospinal Irradiation Versus Photon Involved-Field Radiotherapy for Patients With Solid Tumor Leptomeningeal Metastasis.” Journal of clinical oncology : official journal of the American Society of Clinical Oncology (2022). PMID: 35802849 ↗
L2RCT_PHASE2Cited in: Distant Metastatic Disease
[63]
Yang JC, Wang M, Doucet L et al.. “Phase II Dose-Randomized Study of Sunvozertinib in Platinum-Pretreated Non-Small Cell Lung Cancer With Epidermal Growth Factor Receptor Exon 20 Insertion Mutations (WU-KONG1B).” Journal of clinical oncology : official journal of the American Society of Clinical Oncology (2025). PMID: 40923280 ↗
L2RCT_PHASE2Cited in: Distant Metastatic Disease
[64]
Le X, Patel JD, Shum E et al.. “A Multicenter Open-Label Randomized Phase II Study of Osimertinib With and Without Ramucirumab in Tyrosine Kinase Inhibitor-Naïve EGFR-Mutant Metastatic Non-Small Cell Lung Cancer (RAMOSE trial).” Journal of clinical oncology : official journal of the American Society of Clinical Oncology (2024). PMID: 39378386 ↗
L2RCT_PHASE2Cited in: Distant Metastatic Disease
[65]
Li Z, Hu J, Chen J et al.. “Aumolertinib with or without chemotherapy in EGFR-mutated advanced non-small-cell lung cancer (AENEAS2): an open-label, multicentre, randomised, controlled, phase 3 trial.” The Lancet. Oncology (2026). PMID: 42296979 ↗
L1RCTCited in: Distant Metastatic Disease
[66]
Antonia SJ, Villegas A, Daniel D et al.. “Overall Survival with Durvalumab after Chemoradiotherapy in Stage III NSCLC.” The New England journal of medicine (2018). PMID: 30280658 ↗
L1RCTCited in: Distant Metastatic Disease
[67]
Goldberg SB, Schalper KA, Gettinger SN et al.. “Pembrolizumab for management of patients with NSCLC and brain metastases: long-term results and biomarker analysis from a non-randomised, open-label, phase 2 trial.” The Lancet. Oncology (2020). PMID: 32251621 ↗
L2RCT_PHASE2Cited in: Distant Metastatic Disease
[68]
Goldberg SB, Gettinger SN, Mahajan A et al.. “Pembrolizumab for patients with melanoma or non-small-cell lung cancer and untreated brain metastases: early analysis of a non-randomised, open-label, phase 2 trial.” The Lancet. Oncology (2016). PMID: 27267608 ↗
L2RCT_PHASE2Cited in: Distant Metastatic Disease
[69]
Hui Z, Men Y, Hu C et al.. “Effect of Postoperative Radiotherapy for Patients With pIIIA-N2 Non-Small Cell Lung Cancer After Complete Resection and Adjuvant Chemotherapy: The Phase 3 PORT-C Randomized Clinical Trial.” JAMA oncology (2021). PMID: 34165501 ↗
L1RCTCited in: Distant Metastatic Disease
[70]
Wang HM, Liao ZX, Komaki R et al.. “Improved survival outcomes with the incidental use of beta-blockers among patients with non-small-cell lung cancer treated with definitive radiation therapy.” Annals of oncology : official journal of the European Society for Medical Oncology (2013). PMID: 23300016 ↗
L2PROSPECTIVE_COHORTCited in: Distant Metastatic Disease
[71]
Akamatsu H, Toi Y, Hayashi H et al.. “Efficacy of Osimertinib Plus Bevacizumab vs Osimertinib in Patients With EGFR T790M-Mutated Non-Small Cell Lung Cancer Previously Treated With Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitor: West Japan Oncology Group 8715L Phase 2 Randomized Clinical Trial.” JAMA oncology (2021). PMID: 33410885 ↗
L2RCT_PHASE2Cited in: Distant Metastatic Disease
[72]
Provencio M, Serna-Blasco R, Nadal E et al.. “Minimal Residual Disease Enhances Prognostic Stratification beyond Pathologic Response in Resectable Non-Small Cell Lung Cancer.” Clinical cancer research : an official journal of the American Association for Cancer Research (2026). PMID: 41537692 ↗
L1RCTCited in: Distant Metastatic Disease
[73]
Santini D, Galluzzo S, Vincenzi B et al.. “New developments of aminobisphosphonates: the double face of Janus.” Annals of oncology : official journal of the European Society for Medical Oncology (2007). PMID: 17591815 ↗
L2NON_RANDOMIZED_TRIALCited in: Distant Metastatic Disease
[74]
Park S, Lee MH, Seong M et al.. “A phase II, multicenter, two cohort study of 160 mg osimertinib in EGFR T790M-positive non-small-cell lung cancer patients with brain metastases or leptomeningeal disease who progressed on prior EGFR TKI therapy.” Annals of oncology : official journal of the European Society for Medical Oncology (2020). PMID: 32634610 ↗
L2NON_RANDOMIZED_TRIALCited in: Distant Metastatic Disease
[75]
Le X, Cornelissen R, Garassino M et al.. “Poziotinib in Non-Small-Cell Lung Cancer Harboring HER2 Exon 20 Insertion Mutations After Prior Therapies: ZENITH20-2 Trial.” Journal of clinical oncology : official journal of the American Society of Clinical Oncology (2021). PMID: 34843401 ↗
L2NON_RANDOMIZED_TRIALCited in: Distant Metastatic Disease
[76]
Welsh JW, Komaki R, Amini A et al.. “Phase II trial of erlotinib plus concurrent whole-brain radiation therapy for patients with brain metastases from non-small-cell lung cancer.” Journal of clinical oncology : official journal of the American Society of Clinical Oncology (2013). PMID: 23341526 ↗
L2NON_RANDOMIZED_TRIALCited in: Distant Metastatic Disease
[77]
Chen L, Davelaar J, Gaddam S et al.. “Early Application of Next-Generation Sequencing Identifies Pancreatic Mass as Metastasis From an EGFR-Mutated Lung Adenocarcinoma.” Journal of the National Comprehensive Cancer Network : JNCCN (2022). PMID: 36395704 ↗
L4CASE_SERIESCited in: Distant Metastatic Disease
[78]
Altorki NK, McGraw TE, Borczuk AC et al.. “Neoadjuvant durvalumab with or without stereotactic body radiotherapy in patients with early-stage non-small-cell lung cancer: a single-centre, randomised phase 2 trial.” The Lancet. Oncology (2021). PMID: 34015311 ↗
L2RCT_PHASE2Cited in: Oligometastatic Disease
[79]
Baumann P, Nyman J, Hoyer M et al.. “Outcome in a prospective phase II trial of medically inoperable stage I non-small-cell lung cancer patients treated with stereotactic body radiotherapy.” Journal of clinical oncology : official journal of the American Society of Clinical Oncology (2009). PMID: 19414667 ↗
L2NON_RANDOMIZED_TRIALCited in: Oligometastatic Disease
[80]
Swaminath A, Parpia S, Wierzbicki M et al.. “Stereotactic vs Hypofractionated Radiotherapy for Inoperable Stage I Non-Small Cell Lung Cancer: The LUSTRE Phase 3 Randomized Clinical Trial.” JAMA oncology (2024). PMID: 39298144 ↗
L1RCTCited in: Oligometastatic Disease
[81]
Lee JB, Kim KH, Yoon S et al.. “Lazertinib with stereotactic body radiotherapy in oligometastatic EGFR-mutant non-small-cell lung cancer.” ESMO open (2026). PMID: 41604814 ↗
L2NON_RANDOMIZED_TRIALCited in: Oligometastatic Disease
[82]
Heinzerling JH, Mileham KF, Robinson MM et al.. “Primary lung tumour stereotactic body radiotherapy followed by concurrent mediastinal chemoradiotherapy and adjuvant immunotherapy for locally advanced non-small-cell lung cancer: a multicentre, single-arm, phase 2 trial.” The Lancet. Oncology (2024). PMID: 39615497 ↗
L2NON_RANDOMIZED_TRIALCited in: Oligometastatic Disease
[83]
Theelen WSME, Peulen HMU, Lalezari F et al.. “Effect of Pembrolizumab After Stereotactic Body Radiotherapy vs Pembrolizumab Alone on Tumor Response in Patients With Advanced Non-Small Cell Lung Cancer: Results of the PEMBRO-RT Phase 2 Randomized Clinical Trial.” JAMA oncology (2019). PMID: 31294749 ↗
L2RCT_PHASE2Cited in: Oligometastatic Disease
[84]
Bezjak A, Paulus R, Gaspar LE et al.. “Safety and Efficacy of a Five-Fraction Stereotactic Body Radiotherapy Schedule for Centrally Located Non-Small-Cell Lung Cancer: NRG Oncology/RTOG 0813 Trial.” Journal of clinical oncology : official journal of the American Society of Clinical Oncology (2019). PMID: 30943123 ↗
L4PHASE_1_TRIALCited in: Oligometastatic Disease
[85]
Simpson DR, Sanghvi P, Sandhu AP. “Lung stereotactic body radiotherapy for early-stage NSCLC in patients with prior pneumonectomy: a case report.” Journal of the National Comprehensive Cancer Network : JNCCN (2014). PMID: 25361797 ↗
L4CASE_SERIESCited in: Oligometastatic Disease
[86]
Lee JB, Kim DK, Lee SH et al.. “A Phase II Study of Stereotactic Ablative Radiotherapy plus Atezolizumab plus Tiragolumab in Treatment-Naïve Patients with Advanced Non-Small Cell Lung Cancer.” Clinical cancer research : an official journal of the American Association for Cancer Research (2026). PMID: 42008740 ↗
L2NON_RANDOMIZED_TRIALCited in: Oligometastatic Disease
[87]
Wang Y, Donovan EK, Levine MN et al.. “Stereotactic Versus Conventional Radiotherapy in Medically Inoperable Stage I Non-Small Cell Lung Cancer: A Bayesian Reanalysis of the LUSTRE Randomized Trial.” Clinical lung cancer (2026). PMID: 41997828 ↗
L1RCTCited in: Oligometastatic Disease
[88]
Chmura S, Winter KA, Robinson C et al.. “Evaluation of Safety of Stereotactic Body Radiotherapy for the Treatment of Patients With Multiple Metastases: Findings From the NRG-BR001 Phase 1 Trial.” JAMA oncology (2021). PMID: 33885704 ↗
L4PHASE_1_TRIALCited in: Oligometastatic Disease
[89]
Asami M, Katsumata S, Yasui K et al.. “Comparison of treatment outcomes between stereotactic body radiotherapy/proton beam therapy and sublobar resection for vulnerable elderly patients with stage IA non-small cell lung cancer.” Japanese journal of clinical oncology (2026). PMID: 41215492 ↗
L1RCTCited in: Oligometastatic Disease
[90]
Zhou X, Zhou L, Yao Z et al.. “Safety and Tolerability of Low-Dose Radiation and Stereotactic Body Radiotherapy + Sintilimab for Treatment-Naïve Stage IV PD-L1+ Non-Small Cell Lung Cancer Patients.” Clinical cancer research : an official journal of the American Association for Cancer Research (2023). PMID: 37581611 ↗
L4PHASE_1_TRIALCited in: Oligometastatic Disease
[91]
Adar S, Ádám A, Balogh T et al.. “Sublobar resection, stereotactic body radiotherapy, and thermal ablation for early-stage non-small cell lung cancer: a systematic review and meta-analysis.” Lung cancer (Amsterdam, Netherlands) (2026). PMID: 42202379 ↗
L2SR_COHORTCited in: Oligometastatic Disease
[92]
Zeng H, Wang X, Bai H et al.. “Stereotactic body radiation therapy for ultra-central lung malignancies: an updated systematic review and meta-analysis.” Radiation oncology (London, England) (2026). PMID: 42116164 ↗
L2SR_COHORTCited in: Oligometastatic Disease
[93]
Greto D, Van Hemelrijck M, Oppong F et al.. “Short-term quality of life after metastases-directed SBRT: Results of the ESTRO & EORTC OligoCare cohort.” Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology (2026). PMID: 42314835 ↗
L2PROSPECTIVE_COHORTCited in: Oligometastatic Disease
[94]
Schäfer S, Seiler I, Balermpas P et al.. “Outcome of patients with lung cancer treated with stereotactic body radiotherapy for bone oligometastases - a European multicenter cohort study.” Radiation oncology (London, England) (2026). PMID: 42157246 ↗
L2PROSPECTIVE_COHORTCited in: Oligometastatic Disease
[95]
Zygogianni A, Kougioumtzopoulou A, Platoni K et al.. “Real-World Data on the Safety and Efficacy of SBRT for Central and Ultra-Central Lung Tumors: A Retrospective Multi-Center Cohort.” Cancers (2026). PMID: 41749905 ↗
L4PROSPECTIVE_COHORTCited in: Oligometastatic Disease
[96]
Rakaee M, Andersen S, Giannikou K et al.. “Machine learning-based immune phenotypes correlate with STK11/KEAP1 co-mutations and prognosis in resectable NSCLC: a sub-study of the TNM-I trial.” Annals of oncology : official journal of the European Society for Medical Oncology (2023). PMID: 37100205 ↗
L2PROSPECTIVE_COHORTCited in: Prognosis of Recurrent Disease
[97]
Kelly RJ, Shepherd FA, Krivoshik A et al.. “A phase III, randomized, open-label study of ASP8273 versus erlotinib or gefitinib in patients with advanced stage IIIB/IV non-small-cell lung cancer.” Annals of oncology : official journal of the European Society for Medical Oncology (2019). PMID: 31070709 ↗
L1RCTCited in: Prognosis of Recurrent Disease
[98]
Yoshioka H, Shimokawa M, Seto T et al.. “Final overall survival results of WJTOG3405, a randomized phase III trial comparing gefitinib versus cisplatin with docetaxel as the first-line treatment for patients with stage IIIB/IV or postoperative recurrent EGFR mutation-positive non-small-cell lung cancer.” Annals of oncology : official journal of the European Society for Medical Oncology (2019). PMID: 31553438 ↗
L1RCTCited in: Prognosis of Recurrent Disease
[99]
Reck M, von Pawel J, Zatloukal P et al.. “Overall survival with cisplatin-gemcitabine and bevacizumab or placebo as first-line therapy for nonsquamous non-small-cell lung cancer: results from a randomised phase III trial (AVAiL).” Annals of oncology : official journal of the European Society for Medical Oncology (2010). PMID: 20150572 ↗
L1RCTCited in: Prognosis of Recurrent Disease
[100]
Landreneau RJ, Normolle DP, Christie NA et al.. “Recurrence and survival outcomes after anatomic segmentectomy versus lobectomy for clinical stage I non-small-cell lung cancer: a propensity-matched analysis.” Journal of clinical oncology : official journal of the American Society of Clinical Oncology (2014). PMID: 24982447 ↗
L2PROSPECTIVE_COHORTCited in: Prognosis of Recurrent Disease
[101]
Zhou C, Wu YL, Chen G et al.. “BEYOND: A Randomized, Double-Blind, Placebo-Controlled, Multicenter, Phase III Study of First-Line Carboplatin/Paclitaxel Plus Bevacizumab or Placebo in Chinese Patients With Advanced or Recurrent Nonsquamous Non-Small-Cell Lung Cancer.” Journal of clinical oncology : official journal of the American Society of Clinical Oncology (2015). PMID: 26014294 ↗
L1RCTCited in: Prognosis of Recurrent Disease
[102]
Vansteenkiste JF, Cho BC, Vanakesa T et al.. “Efficacy of the MAGE-A3 cancer immunotherapeutic as adjuvant therapy in patients with resected MAGE-A3-positive non-small-cell lung cancer (MAGRIT): a randomised, double-blind, placebo-controlled, phase 3 trial.” The Lancet. Oncology (2016). PMID: 27132212 ↗
L1RCTCited in: Prognosis of Recurrent Disease
[103]
Spigel DR, Ervin TJ, Ramlau RA et al.. “Randomized phase II trial of Onartuzumab in combination with erlotinib in patients with advanced non-small-cell lung cancer.” Journal of clinical oncology : official journal of the American Society of Clinical Oncology (2013). PMID: 24101053 ↗
L2RCT_PHASE2Cited in: Prognosis of Recurrent Disease
[104]
Kubota K, Yoshioka H, Oshita F et al.. “Phase III, Randomized, Placebo-Controlled, Double-Blind Trial of Motesanib (AMG-706) in Combination With Paclitaxel and Carboplatin in East Asian Patients With Advanced Nonsquamous Non-Small-Cell Lung Cancer.” Journal of clinical oncology : official journal of the American Society of Clinical Oncology (2017). PMID: 28902534 ↗
L2RCT_PHASE2Cited in: Prognosis of Recurrent Disease
[105]
Schild SE, Vokes EE. “Pathways to improving combined modality therapy for stage III nonsmall-cell lung cancer.” Annals of oncology : official journal of the European Society for Medical Oncology (2015). PMID: 26712904 ↗
L2NON_RANDOMIZED_TRIALCited in: Prognosis of Recurrent Disease
[106]
Siena S, Crinò L, Danova M et al.. “Dose-dense temozolomide regimen for the treatment of brain metastases from melanoma, breast cancer, or lung cancer not amenable to surgery or radiosurgery: a multicenter phase II study.” Annals of oncology : official journal of the European Society for Medical Oncology (2009). PMID: 19767314 ↗
L2NON_RANDOMIZED_TRIALCited in: Prognosis of Recurrent Disease
[107]
Matsubara T, Sakamoto T, Takahama T et al.. “Gene testing and prognosis in post-operative recurrent non-small-cell lung cancer: subgroup analyses of WJOG15421L.” ESMO open (2026). PMID: 41922144 ↗
L3RETROSPECTIVE_COHORTCited in: Prognosis of Recurrent Disease
[108]
Altorki N, Wang X, Damman B et al.. “Recurrence of Non-Small Cell Lung Cancer With Visceral Pleural Invasion: A Secondary Analysis of a Randomized Clinical Trial.” JAMA oncology (2024). PMID: 39088196 ↗
L1RCTCited in: Prognosis of Recurrent Disease
[109]
Chang JY, Senan S, Paul MA et al.. “Stereotactic ablative radiotherapy versus lobectomy for operable stage I non-small-cell lung cancer: a pooled analysis of two randomised trials.” The Lancet. Oncology (2015). PMID: 25981812 ↗
L2RCT_PHASE2Cited in: Prognosis of Recurrent Disease
[110]
Kim ES, Neubauer M, Cohn A et al.. “Docetaxel or pemetrexed with or without cetuximab in recurrent or progressive non-small-cell lung cancer after platinum-based therapy: a phase 3, open-label, randomised trial.” The Lancet. Oncology (2013). PMID: 24231627 ↗
L2RCT_PHASE2Cited in: Prognosis of Recurrent Disease
[111]
Samejima H, Kojima K, Shimizu S et al.. “Preoperative low-attenuation area on computed tomography is associated with recurrence after curative resection for non-small-cell lung cancer.” Cancer imaging : the official publication of the International Cancer Imaging Society (2026). PMID: 42210409 ↗
L3bCited in: Workup of Suspected Recurrence
[112]
Li CY, Tsai PC, Hu C et al.. “Maximum standardized uptake (SUVmax) is associated with pathologically upstaged and recurrence-free survival in non-small cell lung cancer after curative surgery.” World journal of surgical oncology (2026). PMID: 42129795 ↗
L4Cited in: Workup of Suspected Recurrence
[113]
Lu Q, Yu J, Zhang Y et al.. “Incorporating intra-fractional delta-radiomics from 4DCT improves local recurrence prediction.” Medical physics (2025). PMID: 41290400 ↗
L3bCited in: Workup of Suspected Recurrence
[114]
Pham D, Thakur N, Park JA et al.. “Computer Assisted Nodule Analysis and Risk Yield Outcomes May be Associated with Recurrence after Stereotactic Body Radiation Therapy in Clinical Stage I Non-Small-Cell Lung Cancer.” Clinical lung cancer (2025). PMID: 41188110 ↗
L3bCited in: Workup of Suspected Recurrence
[115]
Ahn Y, Lee GD, Choi S et al.. “Recurrence Risk Following Percutaneous Transthoracic Needle Biopsy in Patients Undergoing Sublobar Resection for Stage I Lung Cancer.” Radiology (2025). PMID: 41085397 ↗
L3bCited in: Workup of Suspected Recurrence
[116]
Feng Y, Xu Y, Wang J et al.. “Prediction of Early Recurrence After Bronchial Arterial Chemoembolization in Non-small Cell Lung Cancer Patients Using Dual-energy CT: An Interpretable Model Based on SHAP Methodology.” Academic radiology (2025). PMID: 40784844 ↗
L3bCited in: Workup of Suspected Recurrence
[117]
Schuurbiers MMF, Smith CG, Hartemink KJ et al.. “Recurrence prediction using circulating tumor DNA in patients with early-stage non-small cell lung cancer after treatment with curative intent: A retrospective validation study.” PLoS medicine (2025). PMID: 40233104 ↗
L4Cited in: Workup of Suspected Recurrence
[118]
Iguchi T, Kojima K, Hayashi D et al.. “Preoperative Maximum Standardized Uptake Value Emphasized in Explainable Machine Learning Model for Predicting the Risk of Recurrence in Resected Non-Small Cell Lung Cancer.” JCO clinical cancer informatics (2025). PMID: 40043221 ↗
L3bCited in: Workup of Suspected Recurrence
[119]
Yegya-Raman N, Berman AT, Ciunci CA et al.. “Phase 2 Trial of Consolidation Pembrolizumab After Proton Reirradiation for Thoracic Recurrences of Non-Small Cell Lung Cancer.” International journal of radiation oncology, biology, physics (2023). PMID: 37652303 ↗
L2bCited in: Local-Regional Recurrence
[120]
Osta BE, Carlisle J, Steuer C et al.. “A Phase 2 Study of Docetaxel, Ramucirumab, and Pembrolizumab for Patients With Metastatic or Recurrent Non-Small-Cell Lung Cancer (NSCLC) who Progressed on Platinum-Doublet and PD-1/PD-L1 Blockade.” Clinical lung cancer (2022). PMID: 35863963 ↗
L2bCited in: Local-Regional Recurrence
[121]
Zheng L, Wang Y, Xu Z et al.. “Concurrent EGFR-TKI and Thoracic Radiotherapy as First-Line Treatment for Stage IV Non-Small Cell Lung Cancer Harboring EGFR Active Mutations.” The oncologist (2019). PMID: 31040256 ↗
L2bCited in: Local-Regional Recurrence
[122]
Sun B, Brooks ED, Komaki R et al.. “Long-Term Outcomes of Salvage Stereotactic Ablative Radiotherapy for Isolated Lung Recurrence of Non-Small Cell Lung Cancer: A Phase II Clinical Trial.” Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer (2017). PMID: 28259750 ↗
L2bCited in: Local-Regional Recurrence
[123]
Yao Y, Xia X, Zhang L et al.. “Incidence of Radiation Pneumonitis Following EGFR-TKI Combined With Thoracic Radiotherapy in Unresectable Stage III or IV Non-Small-Cell Lung Cancer: A Systematic Review and Meta-analysis.” Clinical lung cancer (2026). PMID: 42561633 ↗
L2aCited in: Oligometastatic Disease
[124]
Miao K, Lei S, Zheng X et al.. “Early Local Treatment Delays Multiple Metastases in Non-Small Cell Lung Cancer With Solitary Distant Metastasis: A Multicenter Retrospective Cohort Study.” MedComm (2026). PMID: 42689138 ↗
L2bCited in: Oligometastatic Disease
[125]
Bourbonne V, Lovinfosse P, Geier M et al.. “Development and external validation of a FDG PET-based radiomics model predicting occult lymph node metastasis in non-small cell lung cancer patients.” European journal of nuclear medicine and molecular imaging (2026). PMID: 41543547 ↗
L2bCited in: Oligometastatic Disease
[126]
Zhang C, Jiang BY, Yan LX et al.. “Neoadjuvant sintilimab plus chemotherapy in EGFR-mutant non-small cell lung cancer (NEOTIDE/CTONG2104): phase II trial and correlative genomic analysis in China.” EClinicalMedicine (2026). PMID: 42256683 ↗
L2bCited in: Oligometastatic Disease
[127]
Cattaneo CG, Chiloiro G, Romano A et al.. “Stereotactic body radiotherapy combined with immunotherapy: a systematic review focus on timing and toxicity profile.” Technical innovations & patient support in radiation oncology (2026). PMID: 42022507 ↗
L2aCited in: Oligometastatic Disease
[128]
Abellan C, Mouraux S, Janett S et al.. “Approaches for Lung Fiducial Markers Insertion in Stereotactic Body Radiotherapy: A Systematic Review and Meta-Analysis.” Journal of bronchology & interventional pulmonology (2026). PMID: 41738525 ↗
L2aCited in: Oligometastatic Disease
[129]
Park J, Kang MK, Lee SY et al.. “Consolidative Hypofractionated Radiotherapy for Oligometastatic Non-Small-Cell Lung Cancer.” Clinical lung cancer (2026). PMID: 42669250 ↗
L3bCited in: Oligometastatic Disease
[130]
Chen Y, Farris M, Choi AR et al.. “KA-TMoE: A Deep Learning Method Using Time-Series CT Radiomics to Predict Post-Radiotherapy Rib Fractures in NSCLC Patients.” International journal of radiation oncology, biology, physics (2026). PMID: 42575323 ↗
L3bCited in: Oligometastatic Disease
[131]
Ebinuma Y, Inoue T, Shirata R et al.. “Dosimetric robustness of tumour- and fiducial-based tracking in Radixact lung stereotactic body radiotherapy: a four-dimensional CT-based simulation using imaging-derived tracking-error scenarios.” The British journal of radiology (2026). PMID: 42503175 ↗
L3bCited in: Oligometastatic Disease
[132]
Zhang Z, Tao X, Ju H et al.. “Adding local gyro-knife radiotherapy to EGFR-TKI improves outcomes in EGFR-mutant NSCLC.” European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology (2026). PMID: 42492466 ↗
L3bCited in: Oligometastatic Disease
[133]
Liu D, Yang S, Chen Y et al.. “Precision Stereotactic Body Radiotherapy for Ultra-Central NSCLC: Tailored Margins Reduce Toxicity Without Compromising Tumor Control.” MedComm (2026). PMID: 42488704 ↗
L3bCited in: Oligometastatic Disease
[134]
Dixon LK, Barber E, Cook A et al.. “Sublobar resection or lobectomy for stage Ia non-small cell lung cancer: a systematic review and meta-analysis.” BMJ open respiratory research (2025). PMID: 41173503 ↗
L1aCited in: Prognosis of Recurrent Disease
[135]
Wu YL, Hochmair M, Yang Y et al.. “Selpercatinib in Early-Stage RET Fusion-Positive Non-Small-Cell Lung Cancer.” The New England journal of medicine (2026). PMID: 42223087 ↗
L1bCited in: Prognosis of Recurrent Disease
[136]
Kim SH, Seong H, Jang H et al.. “EGFR Mutations and Recurrence Outcomes in Resected Non-Small Cell Lung Cancer: An Updated 2015-2025 Systematic Review and Meta-Analysis.” Thoracic cancer (2026). PMID: 42414222 ↗
L1aCited in: Prognosis of Recurrent Disease
[137]
Yang Z, Wang S, Ni J et al.. “Surgery versus definitive radiotherapy after induction immunochemotherapy for stage II and III non-small cell lung cancer: A multicenter, pragmatic analysis.” The Journal of thoracic and cardiovascular surgery (2026). PMID: 41856200 ↗
L2bCited in: Prognosis of Recurrent Disease
[138]
Huang Y, Deng Q, Li J et al.. “Proteomic profiling of early-stage non-small cell lung cancer identifies a high-performance protein signature associated with postoperative recurrence.” Lung cancer (Amsterdam, Netherlands) (2026). PMID: 41581312 ↗
L2bCited in: Prognosis of Recurrent Disease
[139]
Yan X, Zhou S, Hu J et al.. “The long-term avoided recurrences and recurrence-related cost of alectinib for postoperative adjuvant therapy in Chinese patients with early-stage ALK-positive non-small cell lung cancer.” Frontiers in public health (2026). PMID: 41726776 ↗
L2bCited in: Prognosis of Recurrent Disease
[140]
Ling A, Samuel E, Mahendran R et al.. “Molecular-Based Risk Prediction Models for Recurrence After Curative Treatment of Early-Stage Lung Cancer: A Systematic Review and Meta-Analysis.” Thoracic cancer (2026). PMID: 42453006 ↗
L4Cited in: Prognosis of Recurrent Disease
[141]
Lai L, Wang Y, Jiang J et al.. “An integrated multimodal model for early prediction of high-risk recurrence phenotype indicative of poor disease-free survival in stage IA NSCLC: a multicenter study.” Frontiers in immunology (2026). PMID: 42625643 ↗
L3bCited in: Prognosis of Recurrent Disease
[142]
Bharat A, Kurihara C, Chung LI et al.. “Lung Transplant for Refractory Lung-Limited Stage IV Non-Small Cell Lung Cancer.” JAMA (2026). PMID: 42418196 ↗
L3bCited in: Prognosis of Recurrent Disease
[143]
Mitsumata S, Miyahara S, Kaneda S et al.. “Radiofrequency identification-guided localization enables sublobar resection for small and early-stage lung cancer.” Surgical endoscopy (2026). PMID: 42301448 ↗
L3bCited in: Prognosis of Recurrent Disease
[144]
Lula LJ, Costa R, Huang L et al.. “European experience on oncological outcomes of patients with early-stage non-small cell lung cancer and any prior cancer following lobectomy or segmentectomy.” Lung cancer (Amsterdam, Netherlands) (2026). PMID: 42270172 ↗
L3bCited in: Prognosis of Recurrent Disease
[145]
Maeda R, Inomata M, Hazemoto T et al.. “Idiopathic pulmonary fibrosis predicts local recurrence following surgery in patients with non-small cell lung cancer.” Journal of cancer research and clinical oncology (2026). PMID: 42034855 ↗
L3bCited in: Prognosis of Recurrent Disease
[146]
Brascia D, Mangiameli G, Congedo MT et al.. “Immune-inflammatory predictors of early and brain recurrence in young patients with resected non-small cell lung cancer.” Lung cancer (Amsterdam, Netherlands) (2026). PMID: 41671630 ↗
L3bCited in: Prognosis of Recurrent Disease
[147]
Jung W, Cho S, Jeon JH et al.. “Percutaneous Transthoracic Needle Biopsy May Increase Recurrence in Early-Stage Non-Small Cell Lung Cancer: A Propensity Score-Matched Analysis.” Annals of surgical oncology (2026). PMID: 41511595 ↗
L3bCited in: Prognosis of Recurrent Disease
[148]
Allen AJ, Simone CB, Sun K et al.. “Hypofractionated and stereotactic body proton radiotherapy for a high-risk lung cancer cohort: A multi-institutional experience from the proton collaborative group prospective registry.” Clinical and translational radiation oncology (2026). PMID: 42787797 ↗
L2bCited in: Oligometastatic Disease
[149]
Li S, Du F, Leng C et al.. “An exploratory case series of sequential stereotactic body radiotherapy and tislelizumab after platinum-doublet chemotherapy in stage IIIB/C-IV non-squamous NSCLC.” Frontiers in immunology (2026). PMID: 42769251 ↗
L4Cited in: Oligometastatic Disease
[150]
Luo Y, Wang Y, Ren P et al.. “SBRT Plus Nivolumab in Advanced NSCLC: A Phase II Multicenter Study With Exploratory Bone Metastases Subgroup Analysis.” Clinical lung cancer (2026). PMID: 42762599 ↗
L2bCited in: Oligometastatic Disease
[151]
Matsuda M, Komiyama T, Marino K et al.. “Evaluation of cases with over 10 years of follow-up after stereotactic body radiotherapy for Stage I lung cancer.” Practical radiation oncology (2026). PMID: 42810616 ↗
L4Cited in: Oligometastatic Disease
[152]
Lin J, Xu H, Tang J et al.. “Not all major pathological responses are equal: prognostic heterogeneity and risk stratification after neoadjuvant chemoimmunotherapy in resectable NSCLC.” Frontiers in immunology (2026). PMID: 42857111 ↗
L2bCited in: Prognosis of Recurrent Disease
[153]
Kanzaki R, Okami J, Tokunaga T et al.. “Long-term Outcomes of Surgery for Clinical T4 Non-Small Cell Lung Cancer: Implications for Surgical Decision Making in the TNM 9th Edition Era.” Annals of surgical oncology (2026). PMID: 42371323 ↗
L3bCited in: Prognosis of Recurrent Disease
[154]
Xing L, Kato T, Levy A et al.. “AdvanTIG-301: a phase III study of ociperlimab plus tislelizumab and concurrent chemoradiotherapy in stage III unresectable non-small cell lung cancer.” Journal for immunotherapy of cancer (2026). PMID: 42648750 ↗
L1bCited in: Distant Metastatic Disease
[155]
Chen F, Su Y, Zeng X et al.. “Efficacy and safety of first-line chemoimmunotherapy versus chemotherapy alone for advanced pulmonary lymphoepithelioma-like carcinoma: a systematic review and real-world cohort study.” Frontiers in immunology (2026). PMID: 42459654 ↗
L2aCited in: Distant Metastatic Disease
[156]
He Y, Wang Y, Wu G et al.. “Immunotherapy plus chemotherapy improves survival in SMARCA4-deficient NSCLC: a real-world cohort study.” Frontiers in immunology (2026). PMID: 42676634 ↗
L2bCited in: Distant Metastatic Disease
[157]
González-Hernández A, Ríos A, Onieva JL et al.. “Prospective germline exome and machine learning-based risk score identify predictive and prognostic biomarkers of immunotherapy outcomes in advanced non-small cell lung cancer.” Journal of translational medicine (2026). PMID: 42231301 ↗
L2bCited in: Distant Metastatic Disease
[158]
Xu W, Xin Y, Yang X et al.. “Survival benefit of concurrent beta-blocker use in cancer patients treated with radiotherapy: A systematic review and meta-analysis.” Medicine (2026). PMID: 42499029 ↗
L1aCited in: Distant Metastatic Disease
[159]
Zhao Z, Shi W, Yu M et al.. “Programmed-death 1/programmed-death ligand 1 inhibitors plus chemotherapy versus chemotherapy for first-line treatment of advanced driver-gene negative non-squamous non-small cell lung cancer: An updated systematic review and meta-analysis.” Indian journal of cancer (2026). PMID: 42301654 ↗
L1aCited in: Distant Metastatic Disease
[160]
You M, Pan Y, Sun C et al.. “Adjuvant immunotherapy in resectable non-small cell lung cancer with nodal downstaging.” Lung cancer (Amsterdam, Netherlands) (2026). PMID: 42691831 ↗
L3bCited in: Distant Metastatic Disease
[161]
Qiu J, Li S, Ge L et al.. “Prognostic significance of extracapsular extension in patients with non-small cell lung cancer following neoadjuvant chemoimmunotherapy: a retrospective cohort study.” Frontiers in immunology (2026). PMID: 42528975 ↗
L3bCited in: Distant Metastatic Disease
[162]
Chen W, Liang Y, Hou Q et al.. “Risk stratification model based on estimated dose of radiation to immune cells and radiotherapy-related nadir lymphocyte count for predicting the efficacy of consolidation immunotherapy in stage III non-small cell lung cancer.” Frontiers in immunology (2026). PMID: 42495622 ↗
L3bCited in: Distant Metastatic Disease
[163]
Munai E, Sun L, Jike A et al.. “Stereotactic versus whole-brain radiotherapy combined with immunotherapy in driver gene-negative NSCLC with brain metastases: a real-world IPTW analysis.” Frontiers in immunology (2026). PMID: 42440626 ↗
L3bCited in: Distant Metastatic Disease
[164]
Hong Y, Jiang R, Chen S et al.. “Survival outcomes and a prognostic nomogram in EGFR-mutant non-small cell lung cancer with leptomeningeal metastasis: a real-world cohort study.” Journal of neuro-oncology (2026). PMID: 42360664 ↗
L3bCited in: Distant Metastatic Disease
[165]
Tane S, Nomura K, Watanabe T et al.. “Preoperative Predictors of Surgical Complexity After Neoadjuvant Immunochemotherapy in Non-small-cell Lung Cancer.” Annals of surgical oncology (2026). PMID: 42310265 ↗
L4Cited in: Distant Metastatic Disease
[166]
Tao Y, Guo R, Li X et al.. “Prognostic value of 18F-FDG PET/CT metabolic parameters in patients with non-small cell lung cancer who achieved a pathological complete response after neoadjuvant chemoimmunotherapy.” Cancer imaging : the official publication of the International Cancer Imaging Society (2026). PMID: 42237141 ↗
L4Cited in: Distant Metastatic Disease
[167]
Passiglia F, Passaro A, Gariazzo E et al.. “Amivantamab in advanced non-small cell lung cancer with epidermal growth factor receptor exon 20 insertion mutations: Real-world data from the Italian ATLAS Registry.” Cancer (2026). PMID: 42216441 ↗
L3bCited in: Distant Metastatic Disease
[168]
Skribek M, Livanou ME, Vathiotis I et al.. “The brain-lung immunotherapy prognostic (BLIP) Score: a novel robust tool for prognostication in non-small cell lung cancer patients with brain metastases.” British journal of cancer (2026). PMID: 42162362 ↗
L3bCited in: Distant Metastatic Disease
[169]
Wang T, Ouyang B, Chen L et al.. “Focused ultrasound ablation surgery combined with immune checkpoint inhibition in driver-gene wild-type NSCLC with liver metastasis: a feasibility study.” International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group (2026). PMID: 42020933 ↗
L4Cited in: Distant Metastatic Disease
[170]
Plissonneau E, Marchal C, Malouf R et al.. “Perioperative immune checkpoint inhibitors with or without chemotherapy versus placebo with or without chemotherapy in elderly people with localised non-small cell lung cancer.” The Cochrane database of systematic reviews (2026). PMID: 42440312 ↗
L1aCited in: Distant Metastatic Disease
[171]
Taniguchi Y, Tanaka T, Tamiya M et al.. “Clinical Outcomes and Prognostic Factors of ABCP Therapy in EGFR-mutated NSCLC in the Osimertinib Era.” Anticancer research (2026). PMID: 42823148 ↗
L4Cited in: Distant Metastatic Disease
[172]
Ma Y, Xia H, Tan X et al.. “Survival Prediction in Patients With Epidermal Growth Factor Receptor-Mutated Non-small Cell Lung Cancer With Bone Metastases Receiving Icotinib Therapy: A Retrospective Observational Study.” Technology in cancer research & treatment (2026). PMID: 42394601 ↗
L3bCited in: Distant Metastatic Disease

Non-Small Cell Lung Cancer Recurrent and Metastatic Disease